Archive for the ‘Neuropsychology’ Category

the brain is so very awesome…

In Brain imaging, Brain studies, Neurogenesis, Neuropsychology, Neuroscience on Thursday, 17 April 2014 at 15:39



Phillip Seymour Hoffman did not have choice or free will and neither do you.

In ADHD, Anxiety, Brain imaging, Brain studies, Child/Adolescent Psychology, General Psychology, Medicine, Mood Disorders, Neuropsychology, Neuroscience, Psychiatry on Tuesday, 11 March 2014 at 12:37

one of the best things about this subject that i’ve read in a long time.  give it a read. it makes you think.

Phillip Seymour Hoffman did not have choice or free will and neither do you..

Gene Linked to Asperger Syndrome, Empathy

In Autism Spectrum Disorders, Genes, Genomic Medicine, Neuropsychology on Friday, 20 December 2013 at 16:52


Gene Linked to Asperger Syndrome, Empathy

Scientists have confirmed that variations in a particular gene play a key role in the autism spectrum condition known as Asperger Syndrome. They have also found that variations in the same gene are also linked to differences in empathy levels in the general population. 

A study published this month in the journal Molecular Autismconfirms previous research that people with Asperger Syndrome (AS) are more likely to carry specific variations in a particular gene. More strikingly, the study supports existing findings that the same gene is also linked to how much empathy typically shown by individuals in the general population.

The research was carried out by a team of researchers led by Professor Simon Baron-Cohen at the Autism Research Centre at Cambridge University. Asperger Syndrome is an autism spectrum condition. The researchers looked for sequence variations (called single nucleotide polymorphisms or SNPs) in the gene known as GABRB3 in a total of 530 adults- 118 people diagnosed with AS and 412 people without a diagnosis.

The team found that certain SNPs in GABRB3 were significantly more common in people with AS. They also discovered that additional genetic variations in the same gene were linked to scores on an empathy measure called the Empathy Quotient (EQ) in the general population.

AS is diagnosed when a person struggles with social relationships and communication, and shows unusually narrow interests and resistance to change, but has good intelligence and language skills. Most genetic studies of autistic spectrum conditions treat autism as if they are all very similar, whereas in reality there is considerable variation (e.g., in language level and intellectual ability).

Rather than studying people on the autistic condition spectrum, this new study looked only people with AS, as a well-defined subgroup of individuals within this range. The researchers examined the gene GABRB3 which regulates the functioning of a neurotransmitter called gamma-aminobutyric acid (GABA) and which contains a number of SNPs that vary across the population.

The volunteers were tested for 45 SNPs within this key gene. The team had previously found that SNPs in this gene were more common in adults with AS and also showed a relationship with empathy levels and tactile sensitivity (how sensitive people are to being touched) in the general population.


Testing a new sample of volunteers who had not taken part in previous studies, the researchers found that three of the SNPs were again more common in adults with AS, and two different SNPs in the same gene were again related to empathy levels in the general population, confirming that the gene is involved in autism spectrum conditions.

Baron-Cohen said: “We are excited that this study confirms that variation in GABRB3 is linked not just to AS but to individual differences in empathy in the population. Many candidate genes do not replicate across studies and across different samples, but this genetic finding seems to be a solid result. Research now needs to focus on where this gene is expressed in the brain in autism, and how it interacts with other genetic and non-genetic factors that cause AS.”

The team was co-led by Dr. Bhismadev Chakrabarti from the Department of Psychology at Reading University. “Genes play an important role in autism and Asperger Syndrome. This new study adds to evidence that GABRB3 is a key gene underlying these conditions. This gene is involved in the functioning of a neurotransmitter that regulates excitation and inhibition of nerve cell activity so the research gives us vital additional information about how the brain may develop differently in people with Asperger Syndrome,” he said.

Varun Warrier, who carried out the study as part of his graduate research at Cambridge University, added: “The most important aspect of this research is that it points to common genetic variants in GABRB3 being involved in both AS and in empathy as a dimensional trait. Although GABRB3 is not the only gene to be involved in this condition and in empathy levels, we are confident that we have identified one of the key players. We are following this up by testing how much protein GABRB3 produces in the brain in autism, since a genetic finding of this kind becomes more explanatory when we can also measure its function.”

Source: Cambridge University

Retrieved from: http://www.biosciencetechnology.com/news/2013/12/gene-linked-asperger-syndrome-empathy?goback=%2Egde_2514160_member_5819480722708119555#%21

Insomnia and Heart Failure Risk: Something to Lose Sleep Over?

In Neuropsychology, Neuroscience, Psychiatry on Tuesday, 21 May 2013 at 06:55

Insomnia and Heart Failure Risk: Something to Lose Sleep Over?

By: Shelley Wood

Clinical Context

Insomnia can lead to activation of the neuroendocrine system, which in turn may promote a higher risk for cardiovascular disease. The authors of the current study previously used the same study cohort to evaluate the risk for acute myocardial infarction (AMI) associated with insomnia. Their results, which were published in the November 8, 2011, issue of Circulation, demonstrated that mild, intermittent sleep problems were not associated with a higher risk for AMI. However, insomnia almost every night and nonrestorative sleep experienced more than once per week were associated with increases in the risk for AMI of more than 40%.

The current study by Laugsand and colleagues examines whether insomnia can affect the risk for incident heart failure.

Study Synopsis and Perspective

Insomnia symptoms in middle age are strongly associated with the subsequent development of heart failure, a large Norwegian cohort study has found[1]. The analysis, which considered over 54 000 men and women, linked insomnia symptoms and heart failure, even in subjects who had never experienced a coronary event.

While the study does not demonstrate causation, researchers led by Dr Lars E Laugsand (Norwegian University of Science and Technology, Trondheim) say their findings have important implications for patient management and, potentially, reducing progression to heart failure.

“If subsequent studies confirm our findings and if causality is better established, the observed prospective association between insomnia and HF [heart failure] risk could have implications for cardiovascular prevention, since insomnia is an easily recognizable and potentially manageable condition,” the authors write.

Speaking with heartwire , Laugsand stressed that the findings do not have immediate implications for physicians, beyond the fact that sleep is important to good health generally.

“I think cardiologists should talk to their patients about sleep problems, but I think it’s a little too early to say that anything should be implemented in the CV [cardiovascular] risk assessment,” he said. “More research is clearly needed to evaluate the possible underlying mechanisms.”

For example, he continued, the chronic activation of stress responses seen in insomnia could be expected to have an impact on the heart. “Patients who are stressed both at night and during the day have increased BP [blood pressure], increased release of stress hormones, increased heart rate, etc, and all of these factors are related to HF, so that’s a potential link between the neuroendocrine system and the sympathetic nervous system. We cannot say this is the case from our study,” but it’s a plausible link, he said.

Community-Based Analysis

Laugsand et al reviewed baseline data relating to insomnia symptoms from the Nord-Trøndelag Health Study on the 54 279 patients enrolled between 1995 and 1997, none of whom had HF at the study outset. By 2008, 1412 patients had developed heart failure.

In a range of analyses that took into account different factors, such as age, cardiovascular disease risk factors, or psychological factors, insomnia symptoms remained strongly correlated with new-onset heart failure, with more symptoms linked with higher risk. For example, subjects who reported having “difficulty initiating sleep” on “almost every night” had a 27% to 66% risk of developing heart failure (depending on the model used), compared with subjects with no insomnia symptoms. By contrast, patients who reported “difficulty initiating sleep” on a frequent basis, in addition to “difficulty maintaining sleep” and feeling that their sleep was “nonrestorative,” had a risk of heart failure that ranged from two to five times higher than in subjects with no insomnia symptoms.

Women were at an increased risk of having heart failure in relation to certain insomnia risk factors and for cumulative measures of insomnia, compared with men, but Laugsand was reluctant to make much of this observation. “You cannot say from these numbers that insomnia is more dangerous for women than men when it comes to having heart failure,” he said. They have a higher relative risk, but that might be due to their lower baseline risk of HF.”

The next step, said Laugsand, would be a trial treating patients for insomnia to see whether such a strategy could mitigate the development of heart failure.

“That would be the ultimate goal, to do a randomized controlled trial. This study is an observational study and saying anything too firm about causality is difficult,” he cautioned. “But from the studies done in insomnia and other sleep problems, we know that sleep problems affect the physiology of the heart.”


  1. Laugsand LE, Strand LB, Platou, et al. Insomnia and the risk of incident heart failure: A population study. Eur Heart J 2013; DOI: 10.1093/eurheartj/eht019. Available at: http://eurheartj.oxfordjournals.org.

Study Highlights

  • Study data were derived from the Nord-Trøndelag cohort, which reflects the general population of Norway. Study recruitment began in 1995. The current study focused on individuals between 20 and 89 years old without a history of heart failure.
  • Participants completed a thorough examination at the outset of the study, including questions regarding insomnia and the use of hypnotic medications. The insomnia history focused on difficulty falling asleep (early insomnia), waking during sleep (middle insomnia), and nonrestorative sleep. A laboratory assessment was also part of the initial examination.
  • The main study outcome was incident heart failure, which was identified from hospital diagnoses and national death registers.
  • The study analyzed the risk for heart failure associated with insomnia, and researchers adjusted their analyses to account for demographic data and traditional cardiovascular risk factors. Researchers also performed an analysis that accounted for patients’ other chronic diseases.
  • 54,279 participants provided study data. The rates of severe insomnia in the study cohort varied between 2.5% and 8.1%, depending on which domain of insomnia was being queried.
  • Older adults and women were more likely to have insomnia. Insomnia was closely related to depression, anxiety, and the presence of cardiovascular risk factors.
  • During a mean evaluation period of 11.3 years, there were 1412 incident cases of heart failure. 408 of these cases were reported from the death registry.
  • In fully adjusted analyses, including psychiatric diagnoses, the presence of early insomnia, middle insomnia, or nonrestorative sleep individually did not significantly increase the risk for heart failure, even when these symptoms were severe.
  • However, there was a dose-dependent positive effect on the risk for heart failure with a greater number of insomnia symptoms. The presence of 1 insomnia symptom was associated with a hazard ratio (HR) for heart failure of 0.96 (95% [confidence interval] CI, 0.57 – 1.61). Having 2 or 3 of these symptoms was associated with respective HRs of 1.35 (95% CI, 0.72 – 2.50) and 4.53 (95% CI, 1.99 – 10.31).
  • The presence of nonrestorative sleep was associated with a higher risk for incident heart failure among women vs men.
  • Exclusion of cases of heart failure diagnosed early during follow-up failed to significantly alter the main study outcome.

Clinical Implications

  • A previous study of the current cohort of adults found that severe, but not mild, insomnia was independently associated with a higher risk for AMI.
  • In the current study by Laugsand and colleagues, only the presence of multiple insomnia symptoms was significantly associated with a higher risk for incident heart failure.

Retrieved from: http://www.medscape.org/viewarticle/781692

what they eyes say about adhd…

In ADHD, ADHD Adult, ADHD child/adolescent, Child/Adolescent Psychology, General Psychology, Neuropsychology, Psychiatry on Tuesday, 21 May 2013 at 06:51

Eye May Be Key to More Accurate ADHD Diagnosis

Megan Brooks

SAN FRANCISCO — Examining the retina may aid in the diagnosis of attention-deficit/hyperactivity disorder (ADHD), new research suggests.

A small study by investigators at Albert-Ludwigs University of Freiburg, Germany, showed that patients with ADHD displayed significantly elevated “background noise” on a pattern electroretinogram (PERG) compared with their healthy peers.

Altered visual signal processing may be a “neuronal correlate for ADHD,” study presenter Emanuel Bubl, MD, told Medscape Medical News. “If we can replicate this finding, it would be of great clinical importance because it would be an objective marker of ADHD.”

Dr. Bubl presented the study here at the American Psychiatric Association’s 2013 Annual Meeting.

PERG — which is a kin to an electrocardiogram of the retina — provides an electrophysiologic measurement of the activity of the retinal ganglion cells.

“This technique is an easy-to-apply and already well-established instrument in ophthalmology. With adaption, it could be widely used,” Dr. Bubl said.

Inattention and distractability are core symptoms of ADHD, but a “clearcut neuronal correlate is missing. Any attempt to find objective markers of ADHD would be very helpful in this context,” Dr. Bubl said.

Dr. Bubl and colleagues used PERG to measure the response of the retina to a checkerboard visual stimuli in 20 patients with ADHD and 20 healthy control participants.

“An elevated neuronal noise or background firing has been proposed as an underlining pathophysiological mechanism and treatment target. We found evidence for an early alteration in visual perception or signal transmission in patients with ADHD, with significantly elevated neuronal noise (P < .014),” said Dr. Bubl. In particular, neuronal noise significantly correlated with inattention, as measured with the Conners’ Adult ADHD Rating Scale.

“The results might explain why patients with ADHD are easily distracted,” Dr. Bubl added.

With more study, the results could have potentially important clinical implications. “With ADHD, there is a debate about the existence of the disease on the one hand and a growing concern about overdiagnosing ADHD and prescription of medication on the other,” he said.

With PERG, the diagnosis of ADHD could be “objectified by measurable signals, and this would be dramatically helpful in the controversial public discussion.” Use of PERG might also help in determining the effects of methylphenidate or psychotherapy on ADHD.

The authors report no relevant financial relationships.

The American Psychiatric Association’s 2013 Annual Meeting. Abstract SCR02-2. Presented May 18, 2013.

Retrieved from: http://www.medscape.com/viewarticle/804409?src=nl_topic&uac=184795PG

and more dsm-v controversy…

In Child/Adolescent Psychology, DSM-V, Neuropsychology, Psychiatry, School Psychology on Tuesday, 21 May 2013 at 06:48

DSM-V: Past Imperfect

By: Nassir Ghaemi, MD, MPH

 Thoughts on a New DSM

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is here. We might as well pretend that Ronald Reagan is still president. Radical changes were made, with limited scientific evidence, when DSM-III was published in 1980 (the year Reagan was elected); even the tiniest changes, with great scientific evidence, are now the subject of outrage.

For me, DSM-5 is a disappointment. I take no pleasure in making this judgment. I wish I could say that DSM revisions are increasingly scientific and getting us closer to truths. But this simply hasn’t happened.

DSM-5 is a disappointment for me not because it is much different from DSM-IV, but because it is so similar. Almost 2 decades after the fourth revision in 1994, despite thousands of research studies on psychiatric conditions, our profession hardly can bring itself to change anything of importance. The radical bipolar/major depressive disorder (MDD) dichotomy is unchanged and untouchable — the third rail of US psychiatry — despite numerous studies casting doubt on the validity of the MDD definition and providing support for broader definitions of bipolar disorder.

The personality disorder concept was nothing but the description of psychoanalytic speculations in 1980. It has remained basically unchanged, despite little research evidence of validity. Personality traits, one of the most well-proven facts in psychology, were recommended by the DSM-5 task force but vetoed by the American Psychiatric Association Board of Trustees. Science was rejected; psychoanalytic tradition was not.

Clinicians may have assumed that we have scientific validity for most of the approximately 400 diagnoses in DSM-5; we have hardly any validity data for the vast majority of those diagnoses, and we have notable validity evidence for numerous concepts that are excluded.

The claim in the Reagan presidency was that DSM would provide reliability; we could agree on definitions. Then, we would do more research so that definitions would evolve toward better validity. Reliability would lead to validity.

When Bill Clinton was president and DSM-IV was published in 1994, a change happened: DSM became an end in itself. The DSM-IV leadership explicitly stated that unless a very high bar of scientific evidence was reached, no changes were allowed. The bar kept being moved higher and higher for science, and lower and lower for politics. The DSM-IV leadership called it “pragmatism”: DSM changes were made on the basis of what that leadership thought was best for patients, they said, and for the profession.

Reliability had become an end in itself; validity no longer mattered because, in a species of extreme social constructionism, the DSM-IV leadership saw the nosology as a way to influence practice, not as a way to discover causes of and treatments for mental illnesses. (They didn’t bother with the question of how you could practice well if you didn’t find out the causes and treatments of illnesses.)

There were hopes that DSM-5 would be different, with scientifically based changes. But a major backlash came: The DSM-IV leadership opposed changes on “pragmatic” grounds, and many in the larger public criticized DSM on social constructionist grounds, as just a means for psychiatrists to make money and influence people. Major changes became minor, and even the minor ones were often dropped to an appendix for further research, which is likely to be ignored.

After 2 decades of being a loyal follower of DSM, the debates of recent years led me to make a sad but definite conclusion: DSM has caused stagnation in psychiatry. If DSM categories are devised primarily because professional leaders want to achieve some clinical or even economic goals, there is no reason why nature should play along. By being “pragmatic” and not scientific, DSM has doomed biological and pharmacologic research in psychiatry to failure for 2 generations.

Now I see a generational change. The leaders of the DSM-III, -IV, and -5 workgroups are often literally the same people, representatives of the 1970’s/1980’s generation in psychiatry. Some of us in later generations do not venerate DSM as the bible of psychiatry, as it’s often called; we instead question it as theology instead of science. Recently, the leadership of the National Institute of Mental Health (NIMH) reached the same conclusion and stated it forcefully: DSM criteria are not scientifically valid, and patients deserve better.

DSM-5 is out, and clinicians will use it, but unfortunately it represents a failed past. Those of us who grew up in that past, and have seen how it has led us to stand still, are inclined to agree with the NIMH that our future deserves to be different.

Retrieved from: http://www.medscape.com/viewarticle/804102?src=nl_topic&uac=184795PG

Use DSM-5 ‘Cautiously, If at All,’ DSM-IV Chair Advises

By: Pam Harrison

On the eve of the official launch of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Allen Frances, MD, chair of the DSM-IV Task Force and one of the new manual’s staunchest critics, is advising physicians to use the DSM-5 “cautiously, if at all.”

“Psychiatric diagnosis is facing a renewed crisis of confidence caused by diagnostic inflation,” Dr. Frances, Duke University, Durham, North Carolina, writes in a new commentary published online May 17 in the Annals of Internal Medicine.

Unlike the DSM-IV, which held the line against diagnostic inflation, he states, “The DSM-5, the recently published fifth edition of the diagnostic manual, ignored this risk and introduced several high-prevalence diagnoses at the fuzzy boundary with normality.”

For example, the DSM-5 opens the door for patients worried about having a medical illness to be diagnosed with somatic symptom disorder.

Normal grief may be misdiagnosed as major depressive disorder, and the forgetfulness of old age may now be interpreted as mild neurocognitive disorder.

“The already overused diagnosis of attention-deficit disorder will be even easier to apply to adults thanks to criteria that have been loosened further,” Dr. Frances adds.

Other changes in the DSM-5 will allow clinicians to label a child with temper tantrums as having disruptive mood dysregulation disorder, and overeating can now be called binge eating disorder.

Real Danger

The real danger in diagnostic inflation is overdiagnosis and overtreatment of patients who are essentially well, he says.

“Drug companies take marketing advantage of the loose DSM definitions by promoting the misleading idea that everyday life problems are actually undiagnosed psychiatric illness caused by a chemical imbalance and requiring a solution in pill form,” Dr. Frances writes.

“New psychiatric diagnoses are now potentially more dangerous than new psychiatric drugs.”

Quite apart from the risk for overtreatment, however, is the risk of neglecting patients with clear psychiatric illness whose access to care has been sharply reduced by slashed state mental health budgets.

As Dr. Frances points out, only one third of persons with severe depression receive mental health care, and a large percentage of the swollen prison population in the United States is made up of true psychiatric patients who have no other place to go.

More damning, however, is the flawed process by which committee members of the DSM-5 arrived at their expanded diagnoses, in Dr. Frances’ view.

As he states, the DSM-5 did not address professional, public, and press charges that its changes lacked sufficient scientific support and defied clinical common sense.

Field trials produced reliability results that did not meet historical standards, and deadlines were consistently missed, he adds.

The American Psychiatric Association also refused a petition from an independent scientific review of the DSM-5 that was endorsed by more than 50 mental health associations.

Dr. Frances said he personally found the DSM-5 process “secretive, closed, and disorganized.”

“I believe that the American Psychiatric Association (APA)’s financial conflict of interest, generated by DSM publishing profits needed to fill its budget deficit, led to premature publication of an incompletely tested and poorly edited product,” Dr. Frances states.

“The problems associated with the DSM-5 prove that the APA should no longer hold a monopoly on psychiatric diagnosis…. The codes needed for reimbursement are available for free on the Internet.”

The APA declined to comment.

Ann Intern Med. Published online May 17, 2013. Full article

DSM-5: Past Imperfect. Medscape. May 18, 2013.

Retrieved from: http://www.medscape.com/viewarticle/804378DSM-5 Officially Launched, but Controversy Persists

By: Caroline Cassels

SAN FRANCISCO — After more than a decade of development and more than 2 years of frequently searing controversy, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has finally been released.

Here at the American Psychiatric Association’s (APA’s) 2013 Annual Meeting, the APA leadership officially launched the manual, which is widely known by clinicians and patients alike as the “Bible of Psychiatry.”

“This is really an important day. I have been involved with the DSM-5 almost from the beginning, and I have seen the work unfold over the past decade. There have been literally hundreds of people, experts from all over the world, from different disciplines, who have contributed [to the DSM-5],” outgoing APA president Dilip Jeste, MD, told reporters attending a press briefing here.

“What we are seeing is a clinical manual based on the best science available…for today’s patients, this is the best manual that we could develop,” Dr. Jeste added.

Key changes in the new edition include a new chapter organization that shows how mental disorders may relate to one another on the basis of underlying vulnerabilities or symptom characteristics.

In addition, in DSM-5, disorders are organized in the context of age — that is, along a developmental lifespan within each chapter — as well as sex and cultural expectations.

What’s New

According to DSM-5 Task Force chair David Kupfer, MD, although the number of disorders are “about the same” as in the last edition of DSM, several new disorders have been added, including binge eating disorder, disruptive mood dysregulation disorder, and hoarding disorder.

A new section for the manual, Section III, describes several conditions that warrant more research before they can be considered as formal disorders in the main part of the manual.

The changes to the manual are designed to help clinicians more precisely identify mental disorders and improve diagnosis while maintaining the continuity of care.

“We expect these changes to help clinicians better serve patients and to deepen our understanding of these disorders based on new research.”

However, not everyone is as enthusiastic about the manual’s release. Allen Frances, MD, who chaired the DSM-IV Task Force and is among the DSM-5’s staunchest critics, told Medscape Medical News that he is filled with “sadness and worry — and I am not a person usually given to either emotion.”

He added that he is very concerned that the “DSM 5 will result in the mislabeling of potentially millions of people who are basically normal. This would turn our current diagnostic inflation into hyperinflation and exacerbate the excessive use of medication in the ‘worried well.’ ”

“DSM-5 turns grief into Major Depressive Disorder; temper tantrums into Disruptive Mood Dysregulation; the expectable forgetting of old age into Mild Neurocognitive Disorder; worrying about illness into Somatic Symptom Disorder; gluttony into Binge Eating Disorder; and anyone who wants a stimulant for recreation or performance enhancement can claim Attention Deficit Disorder,” he said.

“Don’t Buy It, Don’t Use It”

However, incoming APA president Jeffrey Lieberman, MD, told reporters that the idea that the revisions to the manual will lead to overtreatment is “inaccurate and unwarranted.”

“The DSM is a diagnostic guide that reflects what we currently know about how best to define disorders. How it is applied is something that reflects clinical practice,” he said.

The manual’s diagnostic criteria, he added, are based on the current state of the scientific evidence to “verify the existence of a certain condition that we know to be impairing and distressing and enduring for people,” Dr. Lieberman added.

Dr. Frances also expressed concern that the new manual will divert scarce mental health care resources away from those who need it most.

“While we are overtreating people with everyday problems who don’t need it, we are shamefully neglecting the people with moderate to severe psychiatric problems who desperately do.”

His advice to frontline clinicians regarding the DSM-5? “Don’t buy it, don’t use it, don’t teach it. There is nothing at all official about DSM-5, and the codes for reimbursement are available for free on the Internet or in DSM-IV. APA is price-gouging a badly flawed document, no one need feel captive to it.”

NIMH Blog Not an Indictment of DSM-5?

Dr. Frances is not alone in his criticism of the manual. An April 29 blog post by Thomas Insel, MD, director of the National Institute of Mental Health (NIMH), and published on the NIMH Web site stated that although the upcoming manual is reliable, it lacks validity.

As reported by Medscape Medical News at that time, Dr. Insel pointed out that unlike diagnostic criteria for other diseases, the DSM-5 criteria are based on consensus rather than objective laboratory measures, and he noted that the NIMH will be “re-orienting its research away from DSM-5 categories.”

Toward that end, Dr. Insel went on to announce the launch of the NIMH Research Domain Criteria (RDoC) in a first step toward “precision medicine.”

Following Dr. Insel’s blog post, on May 14, the APA and the NIMH issued a joint statement in which the organizations emphasized the need to work together for the good of patients.

Nevertheless, the statement underscored the fact that the NIMH’s position on the DSM-5 had not changed and that “the diagnostic categories represented in the DSM-IV and the International Classification of Diseases-10 (ICD-10, containing virtually identical disorder codes) remain the contemporary consensus standard for how mental disorders are diagnosed and treated.”

However, Dr. Lieberman, who has since collaborated with Dr. Insel, said that the blog post should not be viewed as an indictment of the DSM-5 but rather as an expression of frustration that psychiatry does not yet have the biologically based diagnostic tools as other areas of medicine.

“Even though his blog was interpreted this way, we don’t think Tom intended to impugn the DSM so much as to say that he wanted to exhort the biomedical research community to try and break new ground that will lead to more dynamic and fundamental changes in psychiatric diagnosis,” said Dr. Lieberman.

The DSM-5 is available immediately in print, and an electronic version will be available later this year.

The American Psychiatric Association’s 2013 Annual Meeting. Opening press conference. May 18, 2013.

Retrieved from: http://www.medscape.com/viewarticle/804410

NIMH abandoning DSM V

In General Psychology, Neuropsychology, Psychiatry on Wednesday, 8 May 2013 at 08:03

National Institute of Mental Health abandoning the DSM

In a potentially seismic move, the National Institute of Mental Health – the world’s biggest mental health research funder, has announced only two weeks before the launch of the DSM-5diagnostic manual that it will be “re-orienting its research away from DSM categories”.

In the announcement, NIMH Director Thomas Insel says the DSM lacks validity and that “patients with mental disorders deserve better”.

This is something that will make very uncomfortable reading for the American Psychiatric Association as they trumpet what they claim is the ‘future of psychiatric diagnosis’ only two weeks before it hits the shelves.

As a result the NIMH will now be preferentially funding research that does not stick to DSM categories:

Going forward, we will be supporting research projects that look across current categories – or sub-divide current categories – to begin to develop a better system. What does this mean for applicants? Clinical trials might study all patients in a mood clinic rather than those meeting strict major depressive disorder criteria. Studies of biomarkers for “depression” might begin by looking across many disorders with anhedonia or emotional appraisal bias or psychomotor retardation to understand the circuitry underlying these symptoms. What does this mean for patients? We are committed to new and better treatments, but we feel this will only happen by developing a more precise diagnostic system.

As an alternative approach, Insel suggests the Research Domain Criteria (RDoC) project, which aims to uncover what it sees as the ‘component parts’ of psychological dysregulation by understanding difficulties in terms of cognitive, neural and genetic differences.

For example, difficulties with regulating the arousal system might be equally as involved in generating anxiety in PTSD as generating manic states in bipolar disorder.

Of course, this ‘component part’ approach is already a large part of mental health research but the RDoC project aims to combine this into a system that allows these to be mapped out and integrated.

It’s worth saying that this won’t be changing how psychiatrists treat their patients any time soon. DSM-style disorders will still be the order of the day, not least because a great deal of the evidence for the effectiveness of medication is based on giving people standard diagnoses.

It is also true to say that RDoC is currently little more than a plan at the moment – a bit like the Mars mission: you can see how it would be feasible but actually getting there seems a long way off. In fact, until now, the RDoC project has largely been considered to be an experimental project in thinking up alternative approaches.

The project was partly thought to be radical because it has many similarities to the approach taken by scientific critics of mainstream psychiatry who have argued for a symptom-based approach to understanding mental health difficulties that has often been rejected by the ‘diagnoses represent distinct diseases’ camp.

The NIMH has often been one of the most staunch supporters of the latter view, so the fact that it has put the RDoC front and centre is not only a slap in the face for the American Psychiatric Association and the DSM, it also heralds a massive change in how we might think of mental disorders in decades to come.

Link to NIMH announcement ‘Transforming Diagnosis’.

Retrieved from: http://mindhacks.com/2013/05/03/national-institute-of-mental-health-abandoning-the-dsm/

transforming diagnosis

In Brain imaging, General Psychology, Neuropsychology, Psychiatry on Wednesday, 8 May 2013 at 07:58


ADHD into adulthood

In ADHD, ADHD Adult, ADHD child/adolescent, Neuropsychology, Psychiatry on Sunday, 7 April 2013 at 07:39

Kids’ ADHD May Continue Into Adulthood

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: March 04, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Childhood attention deficit-hyperactivity disorder (ADHD) may carry over into adulthood in 29% of cases, with a higher risk of other psychiatric disorders, a population-based study showed.

Almost 60% of kids diagnosed with ADHD in the study had at least one other psychiatric disorder at around age 30, which was nearly three times the odds seen among other children followed (P<0.01), according to a report in the April issue of Pediatrics.

Suicide by that age was substantially more common with childhood ADHD as well, although overall mortality wasn’t, wrote William Barbaresi, MD, of Boston Children’s Hospital, and colleagues.

“It is concerning that only a minority of children with ADHD reaches adulthood without suffering serious adverse outcomes, suggesting that the care of childhood ADHD is far from optimal,” they wrote. “Our results also indicate that clinicians, insurers, and healthcare systems must be prepared to provide appropriate care for adults with ADHD.”

The key message is that ADHD shouldn’t be ignored in childhood or adulthood, Rachel Fargason, MD, of the University of Alabama at Birmingham, commented in an interview with MedPage Today.

“There has always been the question of whether childhood ADHD persists into adulthood,” she noted.

Previous studies from the 1980s suggested it did, but by looking at the worst cases — people who presented in psychiatric clinics — rather than the typical child in the general population, Fargason explained.

The study included 5,718 individuals from the same birth cohort in the area around Rochester, Minn., where the Mayo Clinic is based. They were followed to an average age of 27 to 29 years using school and medical records to look for ADHD and other outcomes.

The prospective portion of the study included 367 adults who had childhood ADHD and could have their vital status confirmed.

Seven (1.9%) had died by the time of follow-up, yielding a standardized mortality ratio 1.88-fold higher than seen in the rest of the cohort that didn’t have childhood ADHD.

Although that overall survival impact didn’t reach statistical significance, the difference in suicide did.

The standardized mortality ratio was 3.83 for suicide among childhood ADHD cases versus others (P=0.032).

Notably, five of the seven deaths in the childhood ADHD group occurred in the setting of comorbid substance use and psychiatric disorders.

“This finding suggests the psychiatric comorbidities associated with ADHD may place patients at risk for early death, although the relatively small number of cases precludes a statistical analysis,” the researchers noted.

Childhood ADHD was associated with a 57% rate of one or more other psychiatric disorders at follow-up compared with 35% among controls, for an odds ratio of 2.6 (95% CI 1.8 to 3.8).

The rate was higher for those whose ADHD persisted into adulthood, with an OR 4.8-fold higher than in those whose ADHD didn’t persist (81% versus 47%).

The most common adult psychiatric problems after childhood ADHD were:

  • Alcohol dependence or abuse (26%)
  • Antisocial personality disorder (17%)
  • Substance dependence or abuse (16%)
  • Current or past history of hypomanic episode (15%)
  • Generalized anxiety disorder (14%)
  • Current major depressive episode (13%)

Altogether, only 38% of individuals who had ADHD as a child experienced no mental health problems in adulthood.

Study limitations included use of administrative and school record data to determine childhood ADHD as well as the relatively small number of deaths, which may have limited ability to detect differences in early death risk.

The population studied is primarily a white, middle-class community, which might impact generalizability, Barbaresi’s group added.

“It is possible, if not likely, that the magnitude of the adverse outcomes in this cohort would be even greater in populations with additional challenges such as higher rates of poverty,” they noted.

Retrieved from: http://www.medpagetoday.com/Pediatrics/ADHD-ADD/37637?goback=%2Egde_985117_member_219365690

Barbaresi WJ, et al “Mortality, ADHD, and psychosocial adversity in adults with childhood ADHD: a prospective study” Pediatrics 2013; DOI: 10.1542/peds.2012-2354.

increase in adhd diagnoses…

In ADHD, ADHD Adult, ADHD child/adolescent, Neuropsychology, Neuroscience, School Psychology, Special Education on Tuesday, 12 March 2013 at 11:59

is this because of increased awareness, greater recognition of adhd, better diagnostics and screening, etc. or is it because of the heightened demands put upon all of us in today’s society?  i do believe adhd is a very real diagnosis and can have deleterious effects on the brain if left untreated.  what i can tell you i do see in my work as a school psychologist is some children with a true disability and some very savvy parents (or kids, in some instances) who know that a stimulant will help them meet any increased demands and are able to “get” an adhd diagnosis by going to certain doctors or knowing what to say and what “symptoms” to report.  a comprehensive adhd diagnosis is not an easy one to make and takes way more than a ten-minute session with a pediatrician.  this is one of the reasons i am such a proponent of  the advancements in genome wide association studies, neuroanatomy, neurobiology, etc. that can effectively show differences between a brain with adhd and a brain without adhd, thus, one day hopefully being able to diagnose with more than parent and self-report and some testing.  and, with the large population of untreated adhd or late-diagnosed adhd (so, no treatment until adulthood), we are able to see the effects of no treatment, then getting proper treatment.  

i am a fan of a new book on adhd by cecil reynolds, et al.  it is a comprehensive look at adhd by one of the foremost neuropsychologists today.  http://www.amazon.com/Energetic-Brain-Understanding-Managing-ADHD/dp/0470615168 

there’s my two-cents.  here is the article:

Study Suggests Increased Rate of Diagnosis of Attention-Deficit/Hyperactivity Disorder at Health Plan


Media Advisory: To contact study author Darios Getahun, M.D., Ph.D., call Sandra Hernandez-Millett at 626-405-5384 or email sandra.d.hernandez-millett@kp.org or call Vincent Staupe at 415-318-4386 or email vstaupe@golinharris.com.

CHICAGO – A study of medical records at the Kaiser Permanente Southern California health plan suggests the rate of attention-deficit/hyperactivity disorder (ADHD) diagnosis increased from 2001 to 2010, according to a report published Online First by JAMA Pediatrics, a JAMA Network publication.

ADHD is one of the most common chronic childhood psychiatric disorders, affecting 4 percent to 12 percent of all school-aged children and persisting into adolescence and adulthood in about 66 percent to 85 percent of affected children. The origin of ADHD is not fully understood, but some emerging evidence suggests that both genetic and environmental factors play important roles, the authors write in the study background.

Darios Getahun, M.D., Ph.D., of the Kaiser Permanente Southern California Medical Group, Pasadena, Calif., and colleagues used patient medical records to examine trends in the diagnosis of ADHD in all children who received care at Kaiser Permanente Southern California (KPSC) from January 2001 through December 2010. Of the 842,830 children cared for during that time, 39,200 (4.9 percent) had a diagnosis of ADHD.

“The findings suggest that the rate of ADHD diagnosis among children in the health plan notably has increased over time. We observed disproportionately high ADHD diagnosis rates among white children and notable increases among black girls,” according to the study.

The rates of ADHD diagnosis were 2.5 percent in 2001 and 3.1 percent in 2010, a relative increase of 24 percent. From 2001 to 2010, the rate increased among whites (4.7 percent to 5.6 percent); blacks (2.6 percent to 4.1 percent); and Hispanics (1.7 percent to 2.5 percent). Rates for Asian/Pacific Islanders remained unchanged over time, according to study results.

Boys also were more likely to be diagnosed with ADHD than girls, but the study results suggest that the sex gap for black children may be closing over time. Children who live in high-income households ($70,000 or more) also were at an increased risk of diagnosis, according to the results.

(JAMA Intern Med. Published online January 21, 2013. doi:10.1001/2013.jamapediatrics.401. Available pre-embargo to the media at http://media.jamanetwork.com.)

Retrieved from: http://media.jamanetwork.com/news-item/study-suggests-increased-rate-of-diagnosis-of-attention-deficithyperactivity-disorder-at-health-plan/

preschoolers and adhd…a six-year follow up.

In ADHD, ADHD Adult, ADHD child/adolescent, ADHD stimulant treatment, Neuropsychology, Psychiatry on Wednesday, 6 March 2013 at 16:04


“ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.”

genes, genes…

In ADHD, ADHD Adult, ADHD child/adolescent, Autism Spectrum Disorders, General Psychology, Genes, Neuropsychology, Neuroscience, Personality Disorders, Psychiatry on Friday, 1 March 2013 at 06:15

i love gwas and really feel it will continue to broaden our understanding of psychiatric illnesses and, hopefully, lead to better treatment options.

Five Major Psychiatric Disorders Genetically Linked

By: Caroline Cassels

In the largest genetic study of psychiatric illness to date, scientists have discovered genetic links between 5 major psychiatric disorders.

Investigators from the Cross-Disorder Group of the Psychiatric Genomics Consortium have found that autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia share common genetic risk factors.

Specifically, the results of the genome-wide association study (GWAS) reveal single-nucleotide polymorphisms (SNPs) in 2 genes —CACNA1C and CACNB2 — both of which are involved in the balance of calcium in brain cells, are implicated in several of these disorders, and could provide a potential target for new treatments.

“This analysis provides the first genome-wide evidence that individual and aggregate molecular genetic risk factors are shared between 5 childhood-onset or adult-onset psychiatric disorders that are treated as distinct categories in clinical practice,” study investigator Jordan Smoller, MD, Massachusetts General Hospital, Boston, said in a release.

The study was published online February 28 in the Lancet.

Potential Therapeutic Target

The researchers note that findings from family and twin studies suggest that genetic risks for psychiatric disorders do not always map to current diagnostic categories and that “doubt remains about the boundaries between the syndromes and the disorders that have overlapping foundations or different variants of one underlying disease.”

“The pathogenic mechanisms of psychiatric disorders are largely unknown, so diagnostic boundaries are difficult to define. Genetic risk factors are important in the causation of all major psychiatric disorders, and genetic strategies are widely used to assess potential overlaps,” the investigators write.

The aim of the study was to identify specific variants underlying genetic effects shared between 5 major psychiatric disorders: ASD, ADHD, BD, MDD, and schizophrenia.

The researchers analyzed genome-wide SNP data for the 5 disorders in 33,332 cases and 27,888 control participants of European ancestry. They identified 4 risk loci that have significant and overlapping links with all 5 diseases. These included regions on chromosomes 3p21 and 10q24, and SNPs in the gene CACNA1C,which has previously been linked to bipolar disorder and schizophrenia, and in theCACNB2 gene.

Polygenic risk scores confirmed cross-disorder effects, most strongly between adult-onset disorders BD and MDD and schizophrenia. Further pathway analysis corroborated that calcium channel activity could play an important role in the development of all 5 disorders.

“Significant progress has been made in understanding the genetic risk factors underlying psychiatric disorders. Our results provide new evidence that may inform a move beyond descriptive syndromes in psychiatry and towards classification based on underlying causes.

“These findings are particularly relevant in view of the imminent revision of classifications in the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases,” said Dr. Smoller.

The investigators add that the study results “implicate a specific biological pathway — voltage-gated calcium-channel signalling — as a contributor to the pathogenesis of several psychiatric disorders, and support the potential of this pathway as a therapeutic target for psychiatric disease.”

In an accompanying editorial, Alessandro Serretti, MD, PhD, and Chiara Fabbri, MD, from the University of Bologna, Italy, assert that “the main innovative contribution of the present study is the combination of qualitative and quantitative analyses of the shared genetic features associated with vulnerability of these 5 disorders.”

They add, “the present study might contribute to future nosographic systems, which could be based not only on statistically determined clinical categories, but also on biological pathogenic factors that are pivotal to the identification of suitable treatments.”

The authors and editorialists have reported no relevant financial relationships.

Retrieved from: http://www.medscape.com/viewarticle/779979?src=nl_topic

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis


Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.


We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples.


SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10−8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers.


Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.

Funding-National Institute of Mental Health.

Retrieved from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)62129-1/abstract

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis
Cross-Disorder Group of the Psychiatric Genomics Consortium
The Lancet – 28 February 2013
DOI: 10.1016/S0140-6736(12)62129-1

what causes depression? a possible answer.

In Genes, Genomic Medicine, Mood Disorders, Neuropsychology, Neuroscience, Psychiatry, Psychopharmacology on Thursday, 21 February 2013 at 06:54

Potential Cause of Depression Identified

By: Meagan Brooks

A protein involved in synaptic structure has been identified as a potential cause of depression, a finding that according to researchers has “enormous therapeutic potential for the development of biomarkers and novel therapeutic agents.”

Investigators at the Mount Sinai School of Medicine in New York City found decreased expression of Rac1 in the postmortem brains of people with major depressive disorder (MDD) and in mice subjected to chronic stress. They were able to control the depressive response in mice by manipulating the expression of Rac1.

“Our study is among only a few in depression research in which 2 independent human cohorts and animal models validate each other. Rac1 has enormous therapeutic potential, and I look forward to investigating it further,” study investigator Scott

Looking for Drug Targets

Rac1 is a small Rho GTPase protein involved in modulating synaptic structure.

“There is a hypothesis that depression and stress disorders are caused by a restructuring of brain circuitry,” Dr. Russo explained in an interview with Medscape Medical News.

The scientists subjected mice to repeated bouts of social stress and then evaluated the animals for changes in gene expression in the nucleus accumbens (NAc), the brain’s reward center.

The researchers found that expression of Rac1 was significantly downregulated in the brains of mice for at least 35 days following the end of the chronic social stressor. Rac1 was not affected by only a single episode of stress, indicating that only prolonged stressors that induce depression are capable of downregulating Rac1.

The scientists note that chronic stress in the mice caused epigenetic changes in chromatin that led to Rac1 downregulation.

They were able to control the depressive response to chronic stress to some extent by chronic antidepressant treatment. Histone deacetylase (HDAC) inhibitors were “extremely effective in both normalizing the reduction in Rac1 and also promoting antidepressant responses,” Dr. Russo told Medscape Medical News.

“What we think is happening is that chronic stress leads to a lasting change in the ability of our genes to transcribe this RAC1 gene, and if you target the epigenome, you can reverse that loss of Rac1 and promote synapses and more normal healthy responses,” he said.

As in the mice, Rac1 expression was also strongly downregulated in the NAc in postmortem brains of patients with MDD, who displayed similar epigenetic changes. In most of the individuals with MDD who were taking antidepressants at the time of death, Rac1 expression was not restored to the levels seen in control participants, “suggesting a need for more direct RAC1-targeting strategies to achieve therapeutic effects,” the authors write.

“Currently, there aren’t any approved drugs or even experimental drugs that target Rac1 that are safe and effective,” Dr. Russo said. “It would be nice if we could team up with some chemists or pharma and figure out if there are some safe and effective Rac activators.”

However, there are caveats to that, he said.

“It might be difficult to target Rac specifically, because it is involved in cell proliferation and restructuring so it may be difficult to get a compound that doesn’t cause cancer. It might be better to screen for targets that more generally regulate synaptic plasticity. Ketamine is a drug that does this, and there is huge interest in ketamine” in depression, Dr. Russo said.

Experts Weigh In

Commenting on the findings for Medscape Medical News, David Dietz, PhD, assistant professor of pharmacology and toxicology, State University of New York at Buffalo, who was not involved in the research, said the study “is exquisitely well done. The researchers did an excellent job of translating their findings in the rodent model to the human condition.”

Maria V. Tejada-Simon, PhD, who also was not involved in this research but who has studied Rac1, noted that her group has been “highlighting the importance of Rac1 in the brain in general, and in psychiatric diseases in particular, for a while now. Therefore, I am not surprised that Rac1 has been found to be also associated to stress disorders and depression.”

“Mood disorders have been linked to changes in synaptic structure, and it is certain that small GTPases such as Rac1 have a tremendous role as modulators of these processes. However, we need to understand that alterations in Rac1 signaling are not likely to be the primary defect in mood disorders.

“Thus, targeting Rac1 to moderate clinical symptoms (while there is potential for a translational approach there) has to be done very carefully, given the broad role of Rac1 in many cellular functions involving the actin cytoskeleton,” said Dr. Tejada-Simon, assistant professor of pharmacology and adjunct assistant professor of biology and psychology at University of Houston College of Pharmacy in Texas.

“The highlight of this research is in identifying a possible mechanism by which we can study pathways that are involved in remodeling of the brain; we might be able to find something a little bit more specific down the line,” Dr. Dietz said.

He noted that Rac1 has also been linked to addiction.

“It’s well known that there is comorbidity between depression and addiction, that one may lead to the other, so there seems to be something fundamentally related between Rac1 and these 2 psychiatric disease states.”

The research was supported by the National Institute of Mental Health and the Johnson and Johnson International Mental Health Research Organization Rising Star Award (presented to Dr. Russo). The other authors, Dr. Tejada-Simon, and Dr. Dietz have disclosed no relevant financial relationships.

Nat Med. Published online February 17, 2013. Abstract

Retrieved from: http://www.medscape.com/viewarticle/779544?src=nl_topic

Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression

Sam A Golden, Daniel J Christoffel, Mitra Heshmati, Georgia E Hodes, Jane Magida,Keithara Davis, Michael E Cahill, Caroline Dias, Efrain Ribeiro, Jessica L Ables, Pamela J Kennedy, Alfred J Robison, Javier Gonzalez-Maeso, Rachael L Neve, Gustavo Turecki, Subroto Ghose, Carol A TammingaScott J Russo

Nature Medicine(2013) doi:10.1038/nm.3090; Received 11 October 2012.  Accepted 14 January 2013.  Published online 17 February 2013.


Depression induces structural and functional synaptic plasticity in brain reward circuits, although the mechanisms promoting these changes and their relevance to behavioral outcomes are unknown. Transcriptional profiling of the nucleus accumbens (NAc) for Rho GTPase–related genes, which are known regulators of synaptic structure, revealed a sustained reduction in RAS-related C3 botulinum toxin substrate 1 (Rac1) expression after chronic social defeat stress. This was associated with a repressive chromatin state surrounding the proximal promoter of Rac1. Inhibition of class 1 histone deacetylases (HDACs) with MS-275 rescued both the decrease in Rac1 transcription after social defeat stress and depression-related behavior, such as social avoidance. We found a similar repressive chromatin state surrounding the RAC1 promoter in the NAc of subjects with depression, which corresponded with reduced RAC1 transcription. Viral-mediated reduction of Rac1 expression or inhibition of Rac1 activity in the NAc increases social defeat–induced social avoidance and anhedonia in mice. Chronic social defeat stress induces the formation of stubby excitatory spines through a Rac1-dependent mechanism involving the redistribution of synaptic cofilin, an actin-severing protein downstream of Rac1. Overexpression of constitutively active Rac1 in the NAc of mice after chronic social defeat stress reverses depression-related behaviors and prunes stubby spines. Taken together, our data identify epigenetic regulation of RAC1 in the NAc as a disease mechanism in depression and reveal a functional role for Rac1 in rodents in regulating stress-related behaviors.

Retrieved from: http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.3090.html

the future of neuropsychology…

In Neuropsychology, Neuroscience on Saturday, 26 January 2013 at 07:14

to read or not to read…

In Education, Neuropsychology, Neuroscience, School Psychology on Saturday, 19 January 2013 at 09:25

reading is fundamental!


computerized neuropsychological assessment…

In Brain imaging, Brain studies, Neuropsychology, Neuroscience on Friday, 23 November 2012 at 16:45

this has to be coming soon.  and i will be thrilled.  can you imagine how many opportunities for further research there will be???  yay!



The Mind of Oliver Sacks

In Brain studies, Neuropsychology, Neuroscience on Monday, 19 November 2012 at 12:41

The Mind of Oliver Sacks.

the illustrious “IQ”

In Education, Neuropsychology, School Psychology on Saturday, 10 November 2012 at 10:52

the debate as to what is iq as well as whether or not it can be accurately measured has been around long before i got into this field and i do think it will be around long after i retire.  here is one side…

urther Evidence That IQ Does Not Measure Intelligence

By: Analee Newitz

Every ten years, the average IQ goes up by about 3 points. Psychologist James Flynn has spent decades documenting this odd fact, which was eventually dubbed the Flynn Effect. The question is, does the Flynn Effect mean we’re getting smarter? Not according to Flynn, who argues that the effect simply reveals that IQ measures teachable skills rather than innate ones. As education changed over time, kids got better at standardized tests like the IQ test. And so their scores went up.

But some thinkers cling to the idea that IQ measures an inborn intelligence that transcends culture and schooling. If that’s true, one would expect that the most abstract, “culture free” elements of IQ testing wouldn’t be subject to the Flynn Effect. But they are. And now two psychology researchers have shown why that is.

What Changed Our Minds?

I talked to Florida State psychology researcher Ainsley Mitchum, who has just published a studyin Journal of Experimental Psychology with his colleague Mark Fox. They looked at changes in how people scored the Raven’s Matrices parts of IQ tests, which measure people’s ability to think abstractly. Often these tests involve charts and pattern recognition, and are widely believed to be free of all cultural biases.

Mitchum and Fox were lucky enough to find a report detailing the scores of a group of young people who took the Raven’s Progressive Matrices test in the 1960s, and compared it to scores of young people taking the test now. The results were consistent with the Flynn Effect. “People who got average scores 50 years ago would be below average now,” Mitchum said. But how could this be?

In modern cultures, more emphasis is being placed on abstraction. Students learn algebra at an earlier age than they used to, for instance, but in addition our everyday lives are full of abstractions. Mitchum noted that simply using “folders” on your computer desktop requires a level of abstract thinking that people would rarely encounter in daily life fifty years ago. “This pattern makes you more comfortable breaking away from the surface level features of objects,” Mitchum explained. So a more high-tech culture, combined with differences in education, enhance people’s ability to engage in abstract reasoning.

Test your abstract thinking with a test very similar to Raven’s Progressive Matrices.

Abstraction Is Cultural

Over time, our ability to deal with abstract information is changing. What this means is that abstraction itself is cultural, and it changes over time just as many other aspects of our culture do. It’s very likely that previous generations were more literal-minded in their thinking. They dealt more often with objects in the real world, and had no need to understand things like avatars — icons that represent a real-world object — or how to translate a tiny flick of the wrist into movement on a screen.

Said Mitchum:

Psychologists want to tell you that intelligence measures an essential ability that’s native to people – a real quantity, not something that’s cultural. So they constructed these tests that were designed to not be sensitive to culture [like the Raven’s Progressive Matrices]. But intelligence can’t be looked at as something separate from culture. We argue that the changes in test scores don’t translate into changes in ability. It doesn’t mean we’re evolving into more intelligent people. The data suggest that what’s changing is knowledge. There’s a type of abstract knowledge that people have now in greater numbers. People on average didn’t have that 50 years ago.

Mitchum noted that you can see this transformation far beyond the boundaries of technology. Even the meta-humor you see on television, such as the referential humor on Community, is far more abstract than what people enjoyed in The Three Stooges half a century ago.

If there’s a substantial change in technology in the future, Mitchum believes we’ll see another shift in the way people learn and deal with information “It shouldn’t be surprising to people that when our environment changes rapidly, the way that people deal with information changes with it,” Mitchum said. “We map onto our environment. So what we’re seeing on IQ tests is the footprint of that.”

You Are Probably Not Much Smarter or Dumber Than Anybody Else

If your IQ is largely the result of your environment, what does that say about intelligence itself? Aren’t some of us born with more mental gifts than others? Probably not, said Mitchum. “Neurotypical adults probably don’t differ as much as it seems,” he said. Certainly some people have cognitive deficiencies from head injuries, neurochemical syndromes, and developmental disabilities. But people whose brains are in the typical range probably don’t differ very much in terms of innate mental abilities. What we measure as “intelligence” on IQ tests is mostly environment and experience.

That doesn’t mean IQ tests are useless. In fact, they are very helpful for tracking the way our cultures are shifting over time. These tests are helping us track the way modes of thought are passed on from one generation to the next, mutating as they go.


You can read a PDF of Mitchum and Fox’s paper on IQ scores here.

James Flynn, Are We Getting Smarter? Rising IQ in the Twenty-First Century (Cambridge: Cambridge University Press, 2012)

Retrieved from: http://io9.com/5959058/further-evidence-that-iq-does-not-measure-intelligence

Mending the Brain Through Music

In Brain imaging, Brain studies, Neuropsychology, Neuroscience on Wednesday, 7 November 2012 at 07:45

Mending the Brain Through Music

Bret S. Stetka, MD, Concetta M. Tomaino, MA, DA, LCAT

Editor’s Note: 
From a Darwinian perspective, music is a mystery. It’s unclearwhether the human ability to appreciate a catchy melody conferred some specific evolutionary advantage or was a by-product of more general adaptations involving sound and pattern processing. But what is known is that evidence of music has been found in every documented human culture[1,2] — and that nearly all of us have at least some innate capacity to recognize and process song. The human brain houses a staggeringly complex neuronal network that can integrate rhythm, pitch, and melody into something far greater with, it turns out, significant therapeutic potential.

Research and clinical experience increasingly support music as medicine. Accessing and manipulating our musical minds can benefit numerous psychiatric, developmental, and neurologic conditions, often more effectively than traditional therapies. Dr. Concetta M. Tomaino, along with noted neurologist and author Dr. Oliver Sacks, cofounded the Institute for Music and Neurologic Function to study the effects of music on the brain and neurologic illness in particular. In light of increasing interest in music therapy and accumulating data supporting the approach, Medscape spoke with Dr. Tomaino about how the brain perceives music and the role of the Beatles in treating neurologic disease.


Medscape: Thanks for speaking with us today, Dr. Tomaino. The Institute for Music and Neurologic Function has been integral to our understanding of how the brain processes music, and how music can be used as therapy in certain neurologic conditions. Can you give us some background on the Institute and discuss your role and work there?

Dr. Tomaino: The Institute was incorporated in 1995 to bridge the worlds of neuroscience and clinical music therapy. It grew out of the work of both myself and Dr. Oliver Sacks, with support from CenterLight Health System (formerly Beth Abraham Family of Health Services).

I’m a music therapist by training, with a master’s degree and doctorate in music therapy but also with a strong neuroscience background. Back in the 1970s, I was working in a nursing home and was amazed at how people with end-stage dementia, with little to no cognitive ability or awareness of their surroundings, could still process familiar music. I started wondering whether music could be used as a specific therapy to arouse cognition in patients with severe dementia.

When I came to Beth Abraham in 1980, Oliver Sacks was the attending neurologist and had been asking similar questions about the postencephalitic patients he wrote about in Awakenings, wondering how music and arts affected people who’d lost brain function through disease or trauma. And so we sought each other out and became good friends.

We worked together, him using music to test patients and me clinically applying music to help people recover or improve function. Both of us realized that there was something important going on here, and in the mid-1980s, we began seeking out scientists who could help us study the effects of music on brain function. In 1985, Oliver’s book The Man Who Mistook His Wife for a Hat became popular, and I was president of the American Association for Music Therapy. Our administration took notice of the attention both Oliver and I were receiving from the media and asked whether there was something they could help us do to expand upon our ideas. And so the Institute was formed as a center dedicated to studying music and brain and bridging the clinical and neuroscience communities.

Medscape: Can you speak about the origins of music therapy and how it’s been used over the years?

Dr. Tomaino: The therapeutic aspects of music have been noted in societies for thousands of years; however, interest really grew around the time of World War II, in part because the Works Progress Administration (WPA) program started bringing musicians into veterans hospitals. Doctors and nurses observed that people who seemed to be totally unresponsive would come to life when music was played. The hospital staff wanted to bring more musicians in, but training was needed to prepare them to better understand the conditions and needs of the patients. The approach gained attention, and eventually music therapy came together as a profession in the late 1940s. We now have a certification board, and the American Association for Music Therapy oversees academic and clinical training approaches.

The scope of music therapy has become very broad. It’s been studied and shown effective in psychiatric illness; developmental issues; and medical conditions, including pre- and postoperative settings. However, Dr. Sacks’ and my interests and contributions to the field have been in the area of neurologic function.

Medscape: In which neurologic conditions has music therapy shown the greatest effectiveness?

Dr. Tomaino: There are so many, but one of the most recognized areas is motor initiation in patients with neuromuscular and movement disorders, such as Parkinson disease (PD). Patients with PD often have a slowness of movement and a shuffling gait. Music, specifically highly rhythmic music, has been shown — and there’s quite a bit of supporting data here — to help them in training and coordinating their movements and gait. Music also enhances the length of their stride and improves balance.

Later in the course of PD, cognitive and short-term memory decline are common; in this case, music has been shown to be an effective mnemonic tool, a memory enhancer for remembering basic information — phone numbers, people, addresses, things like that (I’ll get to other forms of dementia in a second). My work and that of some colleagues has also shown that singing and using music to enhance voice and communication is also beneficial for people with PD.

Medscape: Is music therapy used preventatively or symptomatically to address the cognitive component of PD?

Dr. Tomaino: Ideally, it’s started early to help prevent memory decline and create new associative memories early in the disease — linking acquaintances, places, and events, for example, in order to prevent or slow future memory problems and enhance recall. Recent research is really enhancing our knowledge of neuroplasticity. Forming these associations — these new neuronal connections — appears to be neuroprotective.

Recalling Words and Memories

Medscape: Another area researched at the Institute is using music therapy to help patients with nonfluent aphasias recover speech — patients who comprehend language and know what they want to say, but just can’t find the words. How successful has this approach been?

Dr. Tomaino: These are patients who have had damage, such as a stroke, to the Broca region of the brain, in the left frontal lobe. Some do have mild cognitive impairment, but mostly they fully understand what’s being said to them — at least, that’s the case in the patients we work with.

We apply several techniques depending on the patient’s residual skills: for example, can they sing a simple song and tap their finger along with the rhythm. We cue them to sing along with familiar lyrics from memory and help prompt word retrieval by leaving pauses within the lyrics — you leave out a few lyrics in a familiar Beatles song and have the patient try to find the words without losing the beat. This helps a great deal. As the person improves, we move toward a more traditional form of melodic intonation therapy (MIT), focusing on the tone and rhythm or normal speech phrases rather than singing lyrics to songs.

Traditional MIT, developed by a team at the Boston Veterans Affairs Hospital in 1973, is being studying by such neuroscientists as Gottfried Schlaug at Harvard Medical School. A simple, 2-tone sequence — a high and a low pitch — is used to pattern the inflection of speech. It has 4 levels, beginning with humming and tapping short phrases and gradually moving toward a Sprechstimme, or a more normal rhythmic speech with little melodic change.

Patients are asked to repeat single words with the beat and tones, gradually increasing to more complex phrases, such as “Good morning, how are you today?” [Editor’s Note: Imagine each syllable alternating between 2 tones.] The repetition overlaid on the music helps reinforce the patterns of normal speech and helps patients recover words and fluency. Neuroimaging studies indicate compensatory changes in the right frontal lobe areas.

Music therapy is also used to as a psychotherapeutic application in mental illness and can help alleviate stress and anxiety. This has an impact on neurologic function as well; for example, multiple sclerosis symptoms can be exacerbated by stress. Preliminary research shows that music can be an excellent tool for self-relaxation and stress management in these patients. And one of the most fascinating areas in which music is used is dementia and amnesia.

Medscape: Dr. Sacks has written about a number of patients who, despite exhibiting severe amnesia, can remember song lyrics perfectly. What does this say about the neuronal pathways involved in musical memory vs say, declarative memory, our ability to consciously recall information? And what is the therapeutic potential here?

Dr. Tomaino: They are most likely primarily processed by separate brain systems. So a person with dementia or amnesia may not consciously recognize a familiar song, but something in their subconscious knows it’s familiar. There are feelings, emotions, or moments of history in there somewhere. And if they listen to those songs, we’re realizing that sometimes these feelings or the emotions are so strong that they trigger fleeting glimpses of pieces of memory. If we can work with those fleeting moments and build upon them, maybe stronger connections can be made and more memories experienced.

Medscape: Do the memories and recollections last once the music has stopped?

Dr. Tomaino: It depends on the patient. I’ve had a few patients with short-term memory problems in whom using music, and progressing from older memories forward, have then been able to recall recent events. In people with Alzheimer-type dementia, who have seemingly lost the ability to recall past events, music with strong emotional ties and meaning can lead to enduring remembrances and recall.

Medscape: Several case reports — including a recent documentary clip that went viral on YouTube — have demonstrated how effective music can be in helping patients with dementia open up and engage with their environment. How much of this is an actual heightened sense of awareness vs reflexive neurologic activity in response to the music?

Dr. Tomaino: It’s both, depending on the individual. Initially, it’s more reflexive and reactive. But if the musical interventions are provided on a regular basis and for longer periods — 15 minutes, 20 minutes, an hour — we find that their short-term memory and attention improve over time.

We did some studies years ago that were funded by the New York State Department of Health and engaged people with mid- to late-stage Alzheimer disease in music therapy sessions for 1 hour, 3 times a week for 10 months. We found that over time, their awareness of other people improved significantly. Some even recognized those people by name, increased their group interactions, and demonstrated improvement in memory and awareness — they once again knew when it was lunch time.

So yes, in patients with dementia, things that you think are lost forever are retrievable over time with this kind of stimulation. I believe there is now scientific evidence showing this — that when somebody’s engaged in an activity that’s meaningful, it involves regions of their frontal cortex that stimulate short term memory and attention. Then if you can hold somebody’s attention with something that’s meaningful for a long period, the very mechanisms that are breaking down in somebody with dementia are actually being enhanced and activated.

Medscape: Interesting. So, music-based therapies work via a variety of musical qualities, with aspects like rhythm, melody, and emotional familiarity having much different effects, respectively?

Dr. Tomaino: Right. There are totally different mechanisms at work here. The emotional and personal connection is important in dementia, whereas in PD, we’re looking at the person’s ability to perceive and feel the beat. In patients with PD, rhythm is so important and unique to the patient. Instead of just picking a beat and using a metronome, we experiment with different rhythms and rhythmic styles to see what the person responds best to. They have to feel the pulse in order for that pulse to drive their motor function. So when we talk about “music therapy,” we’re talking about components of music, such as rhythm, tone, melody, harmony, song — all of these qualities can be used together or individually to affect the patients with certain conditions.

Who Benefits Most?

Medscape: I’m curious about how an individual’s degree of engagement with music before therapy affects the outcome. Does a person’s musical skill or appreciation come into play? Does a classical violinist benefit most from music therapy? A music critic? A Deadhead?

Dr. Tomaino: Anybody can benefit from music therapy, but their background in music can help or hurt them. Most humans have an affinity for sound and can process it in highly complex ways. However, in certain diseases people may lose this ability, and in fact sound may get so distorted that they have a negative response to it, even if they’d loved music before their injury. This is especially evident in people with damage to the right temporal lobe: These patients often lose their perception of pitch. In fact, I think in Musicophilia, Dr. Sacks writes about a classically trained, professional musician who, after localized brain damage, is a quarter tone off in his perception of pitch.

Medscape: That’s right. And he ended up just tuning his piano up a quarter step!

Dr. Tomaino: Yes! So that’s where the music therapist really has to look at what a person is able to perceive. This patient’s perceptive problem probably wouldn’t have bothered someone who couldn’t tell the difference. With a professional musician, you can imagine that their neural connections to sound and perception are greatly enhanced.

For example, we treated a percussionist who’d had a stroke. The traditional therapy would be to work with the nonaffected side to encourage the intact side of the brain to take over function. For example, a right-handed person would be taught to perform tasks with the left hand. But because percussionists and musicians, by nature of their craft, presumably have stronger bilateral neural representation, we convinced the physical therapist to try working with the affected side of the brain and body. The person was able to regain function. By encouraging the patient to use the affected limb, we try to restore as much function as possible to this limb rather than compensate with the other side.

Medscape: We know that certain areas of the brain are highly dedicated to certain aspects of perception and information processing. The left frontal and temporal lobes are highly involved in speech recognition and production. The occipital cortex processes visual information. But music and sound perception and processing seems to involve numerous regions all over the brain. Can you speak about how the brain perceives and processes music, and how this lends itself to therapeutic applications?

Dr. Tomaino: There are some areas of the brain that are known to be involved in specific aspects of sound processing, mainly through looking at people who have lost certain abilities through certain brain lesions. As I mentioned earlier, patients with a lesion in the right temporal lobe often experience loss of pitch perception. We know that singing is dominant in the right temporal lobe; however, syntax of both speech and music is left dominant. And there are areas on both sides of the brain that inform and coordinate with each other when it comes to music, because music isn’t just one specific skill. That said, music processing is incredibly complex, and as far as I know, a complete map of the areas responsible for music and sound processing doesn’t yet exist.

This complexity is probably why music is so beneficial as a therapeutic tool. It’s processed bilaterally: in the cortex and subcortically, where it stimulates evolutionarily primitive areas of brain function, such as the cerebellum and the basal ganglia. So when a person does have a deficit, there is still some part of the brain functioning properly that is involved in music processing and can be stimulated through sound.

Another interesting aspect here is that in patients with damage to higher cortical regions — those with frontal temporal dementia (FTD) — their appreciation for music may change. Oliver wrote about a classically trained musician who didn’t care for any other types of music; after developing FTD, he starting liking rock and roll.

Functional imaging studies, such as those by Dr. Schlaug that I mentioned earlier, are really helping us understand neural plasticity as well as which areas of the brain are involved in what. You can first isolate the components of music, studying where pitch is processed, and beat, and melody. Then you can put them all together, and it becomes very complex. With functional imaging, it became possible to literally watch the brain work in real time while it listens to music.

Acting, Painting, Listening

Medscape: In reading Musicophilia, one of the things that really fascinated me was the idea that our memory for music is far more high-fidelity than it is for nonmusical creative sensory stimuli. Our recollections of visual art and narrative are often distorted or approximated; however, musical memories and dreams have been proven highly accurate in pitch, melody, mood, and rhythm. How does this distinguish music therapy from other forms of creative arts-based interventions, such as art and drama therapy?

Dr. Tomaino: I should admit that I used to be biased when I sat on the board for the creative arts therapy coalition, because I knew that music — especially the components of music, such as rhythm — could directly affect brain function rather than requiring the interpretation by the arts therapist. I think the big difference is the other arts therapies tend to work psychotherapeutically. And in fact, many music therapists work psychotherapeutically, which can be very effective.

But myself, Dr. Sacks, and a few of our colleagues became interested in the neurologic underpinnings of music and how sound itself could arouse and stimulate basic brain functioning. Whereas art and drama tend toward the emotions and personal associations — a sense of self and ego, and all those areas of psychotherapy — the specific components of music can actually affect brain function in a very measurable, functional way.

Because of this, music therapy is one of the therapies still available to people with devastating diseases, such as Alzheimer disease and neuromuscular conditions, in whom the other creative arts therapies would no longer have a therapeutic benefit. Music can bypass upper-brain processes and higher cognition, as well as stimulate some of the fundamental lower and midbrain areas.

I should say that although we don’t treat psychiatric patients at our facility, so often neurologic and psychiatric illnesses — as well as medical illnesses — are intertwined. So the psychotherapeutic component of our music-based interventions are very important to our patients too.

Medscape: How widely accessible is music therapy, and how many therapists are there in the United States?

Dr. Tomaino: There are close to 6000 music therapists in the United States. It’s not that many, when you think about how many people could benefit from it.

Medscape: Short of having access to a music therapy resource for referral, how can clinicians incorporate music therapy techniques into their practice?

Dr. Tomaino: It’s really great that something so effective is available to everyone. Although it is always important to seek out a professional music therapist first, there are therapeutic applications of music that others can make use of: for example, using personalized music to help someone with Alzheimer disease feel connected, or using rhythmic cues to help increase stride and gait in someone with PD.

And we haven’t even touched on children. Professionals who are working with children with autism-spectrum disorders should really seek out music therapy because it’s been very, very successful with this population. It can be so important in developing early language and motor skills, as well as self-identity and social skills.

I could also see a psychiatrist or social worker who’s having a hard time having a patient open up asking them to bring their favorite piece of music in; it could be an effective entry point into forming a relationship. Speech therapists who have a patient with aphasia can ask the persons to sing.

Likewise, a physical or occupational therapist can use rhythmic cues to help with motor problems. It’s amazing how little rhythm is used in rehabilitation especially in helping people with PD move more effectively. Just remember that each patient responds to different musical cues and rhythms, which requires time to navigate. I’ve talked to a few neurologists who will put on a Sousa march and expect a patient to immediately get up and walk!

Editor’s Note: The American Music Therapy Association’s Website maintains a list of music therapists in the United States, many of whom provide Skype services for remote patients.

Retrieved from: http://www.medscape.com/viewarticle/773401?src=mp

Children With Autism Developmentally Normal at 6 Months

In Autism Spectrum Disorders, Neuropsychology, School Psychology, Special Education on Tuesday, 6 November 2012 at 15:24

Children With Autism Developmentally Normal at 6 Months

Pam Harrison

Infants who go on to develop autism spectrum disorder (ASD) are developmentally normal by the age of 6 months, and the earliest signs of developmental disruption are subtle and not specific to autism, prospective, longitudinal data show.

In the largest prospective, longitudinal study to date comparing children with early and later diagnosis of ASD with children without ASD, Rebecca Landa, PhD, Kennedy Krieger Institute, Baltimore, Maryland, and colleagues found that the earliest signs of developmental disruption in children with ASD are likely to be nonspecific to ASD, such as communication or motor delay.

At 6 months, development within both the early-onset ASD children and those with later-onset ASD was comparable both to each other and to non-ASD control children.

“The standard clinical tools that we use to assess early development are not identifying abnormalities in babies midinfancy that go on and have autism,” Dr. Landa told Medscape Medical News.

“So the assumption that any infant who is going to have autism would be obviously autistic in midinfancy is a myth because this just isn’t happening.”

The study was published online October 30 in Child Development.

Developmental Trajectory

Studying the developmental trajectory of multiple systems — motor, cognitive, social, and language — in the first 3 years of life in children with and without ASD could shed light on the susceptibility of the developing brain to the impact of genetic, epigenetic, and environmental factors in children with ASD.

Therefore, the investigators examined language and motor development in children aged 6 to 36 months and social development from 14 to 24 months, the time during which ASD regression usually occurs.

Participants included 204 infant siblings of children with autism as well as 31 infants with no family history of autism.

The Mullen Scales of Early Learning provided measures of motor and language functioning, and the Communication and Symbolic Behavior Scales Developmental Profile provided measures of 2 social functions related to the diagnostic criteria for ASD.

By 14 months, the early-onset group exhibited significantly lower expressive language and shared positive affect scores than the later ASD group (P < .001 for both endpoints).

By 18 months, the early ASD group also had greater delays in receptive (P < .001) and expressive language development (P = .001) compared with the later-onset group.

Gap Closes

At 24 months, however, “the gap between the Early- and Later-ASD groups had closed, and no differences from the Later-ASD group were detected at subsequent ages,” the investigators write.

These findings indicate that the early-ASD group manifested earlier development disruption, especially as it affected language and social functioning, than children with later-onset ASD but that they were no more severely affected than later-onset ASD children at either 30 or 36 months.

“There are different developmental pathways to ASD,” said Dr. Landa.

Children who manifest symptoms by their first birthday are more globally impaired at 14 months than children who have later manifestations of ASD.

On the other hand, children with later-onset ASD do have some signs of developmental delay at 14 months, but these signs are not specific to ASD and include motor and communications delays.

However, by 36 months, both groups are comparable in their social and developmental characteristics, she added.

“Many pediatricians screen for autism at around 18 months, as the American Academy of Pediatrics recommends, but they don’t continue screening after that,” Dr. Landa said.

“But screening should be repeated through early childhood, and if concerning signs of delay associated with ASD are observed in a child who scores normally on standardized tests, further assessment is warranted.”

Need for Early Intervention

Deborah Fein, PhD, University of Connecticut, in Storrs, told Medscape Medical News that it is important to appreciate that the ASD children included in this study were infant siblings of children with ASD.

As such, “this is not the population at large, so these findings might not be generalizable,” Dr. Fein said

On the other hand, infant siblings of children with ASD are a small enough population that they could be followed very closely throughout their preschool years, and subtle delays in motor or social communication development could be identified.

Other children at risk for ASD, including premature infants or infants who have had obstetric complications, are also at risk for ASD and could be similarly followed, she added.

“There are preclinical signs of ASD, but in a sense, it doesn’t matter because if you know a child has some mild delay in cognitive or motor or social communication function, you still want to deliver early interventions,” she said.

“Then if full-blown autism does emerge, you’ll be on top of it.”

The authors and Dr. Fein have disclosed no relevant financial relationships.

Child Dev. Published online October 30, 2012. Abstract

Retrieved from: http://www.medscape.com/viewarticle/773990?src=nl_topic

The Serotonin Hypothesis, Informed Consent and SSRI Antidepressants

In Medication, Mood Disorders, Neuropsychology, Neuroscience, Psychiatry on Wednesday, 31 October 2012 at 15:36

The Serotonin Hypothesis, Informed Consent and SSRI Antidepressants.

happy birthday, glutamate.

In Medication, Neuropsychology, Neuroscience, Psychiatry, Psychopharmacology, Uncategorized on Wednesday, 31 October 2012 at 15:20

Twenty Five Years of Glutamate in Schizophrenia

Daniel C. Javitt

Schizophr Bull. 2012;38(5):911-913. © 2012 Oxford University Press

Abstract and Introduction


At present, all medications for schizophrenia function primarily by blocking dopamine D2 receptors. Over 50 years ago, the first observations were made that subsequently led to development of alternative, glutamatergic conceptualizations. This special issue traces the historic development of the phencyclidine (PCP) model of schizophrenia from the initial description of the psychotomimetic effects of PCP in the early 1960s, through discovery of the link to N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the 1980s, and finally to the development of NMDA-based treatment strategies starting in the 1990s. NMDAR antagonists uniquely reproduce both positive and negative symptoms of schizophrenia, and induce schizophrenia-like cognitive deficits and neurophysiological dysfunction. At present, there remain several hypotheses concerning mechanisms by which NMDAR dysfunction leads to symptoms/deficits, and several theories regarding ideal NMDAR-based treatment approaches as outlined in the issue. Several classes of agent, including metabotropic glutamate agonists, glycine transport inhibitors, and D-serine-based compounds are currently in late-stage clinical development and may provide long-sought treatments for persistent positive and negative symptoms and cognitive dysfunction in schizophrenia.


The mid-20th century was an exciting period for drug development in psychiatry. Antipsychotics were developed based on the seminal observations of Delay and Deniker and linked to D2 blockade shortly thereafter. By 1971, clozapine, the current “gold standard” treatment for schizophrenia, had already been marketed. Antidepressants were developed based on clinical observations with isoniazid (INH) in the 1950s; benzodiazepines were developed based upon GABA receptor-binding assays in the 1960s; and definitive studies demonstrating efficacy of lithium were performed by the early 1970s. Decades later, these classes of compounds continue to form the core of today’s psychopharmacological armamentarium.

In the midst of this transformational period, initial reports appeared as well for a class of novel sedative agent termed “dissociative anesthetics” exemplified by the molecules phencyclidine (PCP, “angel dust”) and ketamine. In monkeys, these compounds produced behavioral symptoms closely resembling those of schizophrenia, including behavioral withdrawal at low dose and catalepsy at high dose (figure 1). Domino and Luby[1] describe the critical steps by which he and his contemporaries verified the unique clinical effects of these compounds in man. The initial characterizations of PCP as causing a centrally mediated sensory deprivation syndrome and producing electroencephalography changes similar to those in schizophrenia were, in retrospect, particularly critical.

Figure 1.

Effect of phencyclidine (PCP) on behavior in monkey, showing dissociation at low dose (A) and catatonia at high dose (B). From Chen and Weston.12

Although the clinical effects of PCP were well documented by the early 1960s, it took another 20 years to characterize these effects at the molecular level. As described by Coyle,[2] key milestones along the way included the pharmacological identification of the PCP receptor in 1979; demonstration of electrophysiological interactions between PCP and N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the early 1980s followed shortly thereafter by pharmacological confirmation; identification of the glycine modulatory site of the NMDAR in 1987; and confirmation of the psychotomimetic effects of ketamine in the mid-1990s. Although researchers still disagree to the paths leading from NMDAR blockade to psychosis, few currently dispute the concept that NMDAR serve as the molecular target of PCP, ketamine, dizocilpine (MK-801), and a host of other clinical psychotomimetic agents.[2–4]

At their simplest, glutamatergic models predict that compounds stimulating NMDAR function should be therapeutically beneficial in schizophrenia.[2,4] Potential sites for intervention include the glycine/D-serine and redox sites of the NMDAR, as well as pathways regulating glutamate, glycine/D-serine, and glutathione synthesis/release.[4] D-Cycloserine, a partial NMDAR glycine-site agonist, may enhance learning and neural plasticity across a range of disorders, including schizophrenia.[5] In addition to providing new drug targets, glutamatergic models provide effective explanation for the hippocampal activation deficits,[6] positive and negative symptoms, distributed neurocognitive deficits, and sensory processing abnormalities[4] that are critical components of the pathophysiology of schizophrenia.

Since the original description, several variations have been developed with somewhat different treatment predictions. The term “NMDA receptor hypofunction” was originally developed to describe the vacuolization and neurodegeneration seen within specific brain regions following high-dose NMDAR antagonist administration.[7] In animal models, neurotoxic effects of PCP were reversed by numerous compounds, including benzodiazepines and α2 adrenergic agonists that ultimately proved ineffective in clinical studies. Nevertheless, this model may explain the pattern of persistent frontotemporal neurocognitive deficits observed in some ketamine abusers.[8] Subsequent hyperglutamatergic models focused on the excess glutamate release induced by NMDAR antagonists, particularly in prefrontal cortex, and prompted studies with compounds, such as lamotrigine or metabotropic glutamate receptor (mGluR) 2/3 agonists, that inhibit presynaptic glutamate release.[9] GABAergic models focus on NMDAR antagonist-induced downregulation of parvalbumin (PV) expression in interneurons and resultant local circuit level (gamma) dysfunction, and suggest use of subunit selective GABAA receptor modulators.[10]

More than 50 years after the initial characterization of PCP, and 25 years after the identification of NMDARs as the molecular target of PCP, we still do not know whether the novel pharmacology of dissociative anesthetics can be translated into effective clinical treatments. Encouraging small-scale single site studies have been published with NMDAR agonists, but have not yet been replicated in academic multicenter trials. Encouraging phase 2 results have also recently been reported by Roche with glycine transport inhibitors.[4] Nevertheless, phase 3 studies remain ongoing and results cannot be predicted. Additional beneficial effects may be observed in obsessive-compulsive disorder, substance abuse and Parkinsons disease.[4] Conversely, NMDAR antagonists, such as ketamine, may be therapeutically beneficial in treatment-resistant depression or autism, suggesting complementary pathology across a range of disorders.[11] More than anything else, 50 years of research shows that treatment development in neuropsychiatric disorders is a journey and not a destination, although fortunately one where the end now finally seems in sight.

Retrieved from: http://www.medscape.com/viewarticle/771599?src=nl_topic


  1. Domino EF, Luby ED. Phencyclidine/schizophrenia: one view toward the past, the other to the future Schizophr Bull. 2012.In press.
  2. Coyle JT. The NMDA receptor and schizophrenia: a brief history Schizophr Bull. 2012.In press
  3. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia Am J Psychiatry 1991 148 1301–1308
  4. Javitt DC. Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophr Bull In press.
  5. Goff D. D-cycloserine: an evolving role in learning and neuroplasticity in schizophrenia.Schizophr Bull In press.
  6. Tamminga CA, Southcott S, Sacco C, Gao XM, Ghose S. Glutamate dysfunction in hippocampus: relevance of dentate gyrus and ca3 signaling.Schizophr Bull. 2012. In press
  7. Olney JW, Newcomer JW, Farber NB. NMDA receptor hypofunction model of schizophrenia J Psychiatr Res.1999 33 523–533
  8. Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study Addiction 2010 105 121–133
  9. Moghaddam B, Krystal JH. Capturing the angel in angel dust: twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans Schizophr Bull. In press.
  10. Lewis DA, Gonzalez-Burgos G. NMDA receptor hypofunction, parvalbumin-positive neurons and cortical gamma oscillations in schizophrenia. Schizophr Bull In press.
  11. Javitt DC, Schoepp D, Kalivas PW, et al. Translating glutamate: from pathophysiology to treatment. Sci Transl Med. 2011;3:102mr102.
  12. Chen GM, Weston JK. The analgesic and anesthetic effects of 1-(1-phenylcyclohexyl)-piperidine HCl in the monkey Anesth Analg. 1960 39 132–137

Area of the Brain that Processes Empathy Identified

In Brain imaging, Brain studies, Neuropsychology, Neuroscience on Sunday, 28 October 2012 at 08:49

Area of the Brain that Processes Empathy Identified

ScienceDaily (Oct. 24, 2012)

An international team led by researchers at Mount Sinai School of Medicine in New York has for the first time shown that one area of the brain, called the anterior insular cortex, is the activity center of human empathy, whereas other areas of the brain are not. The study is published in the September 2012 issue of the journal Brain.

Empathy, the ability to perceive and share another person’s emotional state, has been described by philosophers and psychologists for centuries. In the past decade, however, scientists have used powerful functional MRI imaging to identify several regions in the brain that are associated with empathy for pain. This most recent study, however, firmly establishes that the anterior insular cortex is where the feeling of empathy originates.

“Now that we know the specific brain mechanisms associated with empathy, we can translate these findings into disease categories and learn why these empathic responses are deficient in neuropsychiatric illnesses, such as autism,” said Patrick R. Hof, MD, Regenstreif Professor and Vice-Chair, Department of Neuroscience at Mount Sinai, a co-author of the study. “This will help direct neuropathologic investigations aiming to define the specific abnormalities in identifiable neuronal circuits in these conditions, bringing us one step closer to developing better models and eventually preventive or protective strategies.”

Xiaosi Gu, PhD, who conducted the research in the Department of Psychiatry at Mount Sinai, worked with researchers from the United States and China, to evaluate Chinese patients, at Beijing Tiantan Hospital, who were shown color photographs of people in pain. Three patients had lesions caused by removing brain tumors in the anterior insular cortex; nine patients had lesions in other parts of the brain and 14 patients (the controls) had neurologically intact brains. The research team found that patients with damage restricted to the anterior insular cortex had deficits in explicit and implicit empathetic pain processing.

“In other words, patients with anterior insular lesions had a hard time evaluating the emotional state of people in pain and feeling empathy for them, compared to the controls and the patients with anterior cingulate cortex lesions.” said Dr. Jin Fan, corresponding author of this study and an assistant professor at the Department of Psychiatry at Mount Sinai.

According to Dr. Gu, this study provides the first evidence suggesting that the empathy deficits in patients with brain damage to the anterior insular cortex are surprisingly similar to the empathy deficits found in several psychiatric diseases, including autism spectrum disorders, borderline personality disorder, schizophrenia, and conduct disorders, suggesting potentially common neural deficits in those psychiatric populations.

“Our findings provide strong evidence that empathy is mediated in a specific area of the brain,” said Dr. Gu, who now works at University College London. “The findings have implications for a wide range of neuropsychiatric illnesses, such as autism and some forms of dementia, which are characterized by prominent deficits in higher-level social functioning.”

This study suggests that behavioral and cognitive therapies can be developed to compensate for deficits in the anterior insular cortex and its related functions such as empathy in patients. These findings can also inform future research evaluating the cellular and molecular mechanisms underlying complex social functions in the anterior insular cortex and develop possible pharmacological treatments for patients.

The study was funded by the National Institute of Health, the James S. McDonnell Foundation and a Brain and Behavior Research Foundation NARSAD young investigator award.

Retrieved from: http://www.sciencedaily.com/releases/2012/10/121024175240.htm?utm_source=twitterfeed&utm_medium=linkedin&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain%2Fdisorders_and_syndromes+%28ScienceDaily%3A+Mind+%26+Brain+News+–+Disorders+and+Syndromes%29



Anterior insular cortex is necessary for empathetic pain perception

Xiaosi Gu,  Zhixian Gao, Xingchao Wang, Xun Liu,  Robert T. Knight,  Patrick R. Hof, and

Jin Fan


Empathy refers to the ability to perceive and share another person’s affective state. Much neuroimaging evidence suggests that observing others’ suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are ‘necessary’ for empathetic pain remains unknown. Herein, we examined the perception of others’ pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others’ pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.

Retrieved from: http://brain.oxfordjournals.org/content/135/9/2726

dream a little dream of me…

In Neuropsychology, Neuroscience, Psychiatry, Psychopharmacology on Tuesday, 23 October 2012 at 09:51

What Physicians Need to Know about Dreams and Dreaming

James F. Pagel


Purpose of review: An overview of the current status of dream science is given, designed to provide a basic background of this field for the sleep-interested physician.

Recent findings: No cognitive state has been more extensively studied and is yet more misunderstood than dreaming. Much older work is methodologically limited by lack of definitions, small sample size, and constraints of theoretical perspective, with evidence equivocal as to whether any special relationship exists between rapid eye movement (REM) sleep and dreaming. As the relationship between dreams and REM sleep is so poorly defined, evidence-based studies of dreaming require a dream report. The different aspects of dreaming that can be studied include dream and nightmare recall frequency, dream content, dreaming effect on waking behaviors, dream/nightmare associated medications, and pathophysiology affecting dreaming.

Summary: Whether studied from behavioral, neuroanatomical, neurochemical, pathophysiological or electrophysiological perspectives, dreaming reveals itself to be a complex cognitive state affected by a wide variety of medical, psychological, sleep and social variables.


As most individuals experience the cognitive mentation that we call dreams during sleep, any physician treating sleep needs to have at least a basic understanding of dreaming. It was just 50 years ago that polysomnography allowed for sleep to be electrophysiologically staged. Although sleep had yet to be examined, a huge literature existed on dreaming and, through psychoanalysis, the use of dreams in the treatment of the spectrum of mental illness. Today, the scientific study of dreams has come full circle. We now know a huge amount about sleep, its associated pathophysiology, and treatment, yet what we know scientifically about the dream state is far less than what we thought we knew a generation ago. Much older work was not evidence based, and was methodologically limited by lack of definitions, small sample size, and the constraints of theoretical perspective. After 50 years of dogmatic insistence that rapid eye movement (REM) sleep is dreaming, most researchers in the field now accept that the evidence is overwhelming that REM sleep occurs without dreaming and dreaming without REM sleep.[1] Evidence remains equivocal as to whether any special relationship exists between REM sleep and dreaming.[2•] It is unclear as to what part, if any, of the highly developed neuroanatomical and neurochemical model for REM sleep is applicable to the cognitive state of dreaming.

Definitions: What is a Dream?

Early in the 20th century, Sigmund Freud and his adherents developed the psychoanalytic techniques of free association and dream analysis for use in diagnosing and treating individuals with psychiatric illnesses. Freud focused on the psychopathologic associations of bizarre and unusual dreams, eventually giving us a definition of dreaming as ‘wish fulfillment.’ Psychoanalysts stretched the definition of dreaming to include parasomnias and the REM sleep-associated states of narcolepsy, defining dreams as bizarre, hallucinatory mental activity that can occur in either sleep or wake.[3] This psychoanalytic definition of dreaming became the generally accepted definition for this phenomenon among many psychiatrists and neuroscientists.

From its initial discovery, REM sleep = dreaming was proof of the correlate between psychoanalysis and brain structure, a postulate at the basis of grand theories of dreaming including Activation, Input, Modulation (AIM), now termed protoconsciousness theory and the most developed and widely accepted theory of central nervous system (CNS) functioning.[4] It is a primary postulate of AIM that the neurons and neurochemicals that modulate REM sleep alter dreaming and other conscious states in a similar manner. The AIM model has been adopted and extended into proposals that REM sleep dreaming is the process that organizes neural nets in higher cortical regions.[5] These theories postulate that the cognitive activity of dreaming is based on the CNS activation associated with REM sleep, with dreaming an upper cerebral cognitive process utilizing the CNS activation associated with a primitive electrophysiological state of activation that we call REM sleep. If REM sleep is dreaming, animal models and scanning studies of REM sleep as reported in the popular and scientific press can be construed to be studies of the cognitive state of dreaming. Such studies must be considered suspect, however, as dreaming occurs throughout sleep in forms (except for nightmares) indistinguishable from REM sleep dreaming.[6]

Most sleep medicine physicians consider dreaming to be mentation reported as occurring in sleep by a human participant. This definition contradicts the psychoanalytic definition for dreaming, restricting dreaming to sleep irrespective of content. This definition also differs from the REM sleep = dreaming model in requiring a dream report. Because of this conflation of contradicting definitions, it is important for anyone interested in perusing either scientific or popular literature to note what the author may be referring to in any discussion of dreams and dreaming.[7]

Evidence-based Research Into Dreaming

Characteristics of the dream state amenable to scientific study include recall, content, dream incorporation into waking, and associated pathophysiology.

Dream Recall

Collection methodology including time since waking, process, and defined state characteristics affect reported dream recall frequency. Sleep stage of origin is a primary variable known to affect dream recall frequency. Multiple studies indicate that dream recall reported from REM sleep and sleep onset is in the range of 80%. Although recall from stage 2 varies through the night, recall approximates the 40% recall from stage 3.[8] Recall is generally higher for women and in the young.[9] Increased dream salience and intensity, typical of nightmares, also results in an increase in recall. Significant subjective and objective insomnia is associated with diminished dream recall.[10] Bi-basilar frontal CNS damage can be associated with a loss of dreaming.[11] Although some individuals report that they do not dream, most have experienced dreams at some point in their lives. The much smaller percentage of sleep laboratory patients that have never experienced dreaming (0.038%) do not report dreams in the laboratory when awakened from either REM sleep or non-REM sleep.[12] Despite their lack of dream recall, these individuals have no obvious memory impairment and function normally in our society.

Dream Content

Guttenberg’s first printed book was the Bible, but his second was the Oneirocritica, an interpretation of the meaning of dream symbols.[13] Mankind’s focus on dream content likely predates the development of either printing or writing.[2•] Dream content has been incorporated into the worlds’ major religions, philosophies, literature, and science. The argument can cogently be made that the structure and narrative form of language itself is derived from our attempts to organize and share our dreams. Most dreams are narratives occurring, and often presented without applied organization, grammar, or expectation of critique. In the dream, we can literally observe the ‘thinking of the body,’ and with it, the birth of the literary process. Our dreams can be considered an exercise in pure storytelling whose end is nothing more (or less) than the organization of experience into set patterns that help to maintain order for the thinking system.[14]

Freud postulated that an individual’s psychic structure could be inferred from information derived from the associative interpretation of dreams, and then could be utilized in developing a therapeutic plan for the treatment of psychiatric symptoms.[15] He stated, ‘Psychoanalysis is related to psychiatry approximately as histology is related to anatomy’.[16] For more than a generation, psychiatrists were trained in the method, with the data derived from psychoanalytic techniques used to make diagnoses and form treatment plans. Although psychoanalysis was utilized with occasional success in treating psychiatric illness, most of the evidence attesting to its therapeutic efficacy was anecdotal and subjective.[3]

More recent studies of dream content have attempted to address the significant methodological problems of transference, collection and interpretation that led to the nonreplicable characteristics of dream content studies. Methodologically sound studies have been developed that utilize computerized analysis of the validated Hall and Van de Castle content system.[17] Such studies have shown few, if any, significant differences in dream content between personality types, psychopathologic diagnoses, or socio-ethnic groups.[18] The primary significant correlate for dream content has proven to be waking experience, supporting the so-called continuity hypothesis – dream content reflects our waking experience.[18] Dream researchers have persisted in developing alternative content scales in order to support theoretical perspectives.[19] Although few of these scales have been validated or subjected to independent analysis, the best data is for Hartmann’s analysis of personality correlates (boundaries) that affect both dream recall frequency and content.[20]

Studies have also started to address other aspects of dream content. Visual imagery, the primary characteristic of most reported dreams, follows an operative pattern in dreaming that can be studied and applied externally to filmmaking methodology.[6] Memories follow characteristic patterns in both dream-associated sleep and varied waking states.[21•] Emotions, particularly negative emotions, are routinely incorporated into dreaming.[22]

Dream Incorporation Into Waking Behavior

Many individuals use their dreams. As in recall, dream-use tends to be sex-based and age-based (higher in women and the young).[23] Although ethnic and cultural differences in dream-use exist, such variations do not tend to be present in general population samples.[24] Dream use is significantly higher among individuals reporting creative interests.[25] Among successfully creative individuals, dream and nightmare recall, as well as dream incorporation into work and waking behavior is much higher than in the general population, suggesting that one function of dreaming may be in the creative process.[6,26]

Medications Inducing Disturbed Dreaming and Nightmares

Until recently, neurochemists interested in dreaming focused their studies on the effects of various neurochemicals on REM sleep based on the belief that medications affecting dreaming would be the same ones known to affect REM sleep. Acetylcholine is the primary neuromodulator affecting REM sleep.[27] A wide variety of pharmaceutical agents have anticholinergic activity, and the reported side effects of some of these agents include nightmares, disordered dreaming and hallucinations. This has led some authors to postulate that cholinergic effects of medications induce nightmares, hallucinations, and psychosis.[28] Based on this theoretical construct, the anticholinesterase agents in widespread use for the treatment of the cognitive effects of Alzheimer’s disease should alter dreaming. These agents, however, are reported to induce the side effect of disturbed dreaming or nightmares in only 0.4% of clinical trial participants.[29]

Agents that suppress REM sleep such as ethanol and benzodiazepines induce episodes of REM sleep rebound on withdrawal. These REM sleep rebound episodes have been associated with reports of nightmares and disturbed dreaming, and were considered the primary mechanism for drug-induced disordered dreaming and nightmares. However, nightmares and disordered dreaming are often reported as part of the withdrawal syndrome from addictive medications such as cannabis, cocaine and opiates that, which are not known to affect REM sleep. This suggests that during withdrawal from addictive agents, disturbed dreaming and nightmares may be an intrinsic part of that process rather than occurring secondary to REM sleep rebound.[29,30]

Data based on clinical trials and case reports of effects and side effects of clinically utilized pharmaceutical agents indicate that a much different pattern of medications induce disordered dreaming and nightmares than those known to affect REM sleep.[29] The spectrum of medications affecting dreaming indicates that the state is neurochemically complex with medications influencing the neurotransmitters/neuromodulators dopamine, nicotine, histamine, GABA, serotonin, nicotine, and norepinephrine altering dreaming and reported nightmare frequency in 1–5% of patients using these medications.[29] Medications with clinical cognitive effects and/or side-effects of arousal (insomnia) and/or sedation are those that most commonly alter the reported frequency of disordered dreaming and nightmares ( ).

Among drug classes of prescription medications in clinical use, β-blockers affecting norepinephrine neuroreceptors are most likely to result in patient complaints of disturbed dreaming. The strongest clinical evidence for a specific drug to induce disordered dreaming or nightmares is for the selective serotonin reuptake inhibitor paroxetine – a medication known to suppress REM sleep. Because of the high frequency of use of over-the-counter preparations containing type-1 antihistamines for sleep induction and the treatment of allergies, such preparations are likely responsible for most reports of drug-induced disordered dreaming and nightmares.[29]

Table 1.  Cognitive effects and side effects of medications: neurotransmitter/neuromodulator-associated central nervous system effects

Basis for central nervous system activity Sleepiness Insomnia Alterations in dreaming
Neuromodulator and/or neurotransmitter mediated effects
   Serotonin +++ ++ +++
   Norepinephrine ++ ++ +++
   Dopamine +++ +++ +++
   Histamine +++ + ++
   GABA +++ + ++
   Acetylcholine ++
   Adenosine + +++
   Nicotine +++ +++
Other medication effects
   Effects on inflammation ++ ++ ++
   Addictive drug withdrawal + +++ +++
   Altered conscious interaction with environment +++ + ++
   Alterations in sleep associated disease +++ +++ +

+++, majority of drugs with this activity cause this effect in more than 5% of patients; ++, some drugs with this activity induce this effect in 1–5% of patients; +, an idiosyncratic effect for some agents in this group or withdrawal effect; −reported in less than 1% of patients using agents affecting this neurotransmitter/neuromodulator [29]

Pathophysiology of Dreaming And Nightmares

Although changes in dreaming are sometimes reported, most reports of pathophysiological correlates for dreaming are reports of nightmares – coherent dream sequences usually occurring in REM sleep that become increasingly more disturbing as they unfold and usually resulting in awakening.[31]

Dream-like Parasomnias

Dreaming (cognitive narrative, feeling, or awareness of dreaming on awakening) occurs in association with many parasomnias – unwanted behaviors occurring during sleep.

Parasomnias are in general classified based on sleep stage of origin.

Disorders of Arousal

The disorders of arousal occurring out of deep sleep are associated with dream mentation up to 40% of the time. Somambulism is characterized by autonomic and inappropriate behaviors, frantic attempts to escape a perceived threat, and fragmentary recall. Sleep terrors and confusional arousals are associated with incoherent vocalizations, intense autonomic discharge, confusion and disorientation, and fragmentary dream recall.[32]

Hypnogognic Phenomena

The sleep onset nightmares typical of posttraumatic stress disorder (PTSD) and sleep onset sleep paralysis can occur without the classic REM sleep association. Sleep onset PTSD nightmares often induce distress that interferes with the initiation of sleep. Hypnogogic hallucinations are primarily visual and have coherent dream storylines that are perceived as potentially real. Although commonly experienced (prevalence rates vary from 25 to 37%), such experiences are also a part of the classic tetrad of narcolepsy.[33] The regularly experienced hypnogogic hallucinations reported by 40–60% of individuals carrying the diagnosis of narcolepsy with cataplexy may have more complex storylines than those reported in the general population.[3,34] Sleep starts, most commonly experienced at sleep onset, can be associated with the impression of falling.

Rapid Eye Movement Sleep-associated Parasomnias 

REM sleep is classically associated with dream-like parasomnias. Some of these parasomnias can also occur outside REM sleep. PTSD nightmares and sleep paralysis can occur at sleep onset. REM sleep behavior disorder (RBD) phenomena can also occur in association with arousal disorders.

Nightmare Disorder

Nightmare disorder is characterized by recurrent nontrauma-related REM sleep dreams that result in intense anxiety, fear or terror, and a coherent dream story usually involving imminent physical danger for the dreamer. Associated insomnia and difficulty returning to sleep are usually present. As in most parasomnias, arousals associated with obstructive sleep apnea (OSA) or periodic limb movement disorder can result in increased symptomatology; however, in patients with the disordered sleep associated with moderate to severe OSA, normal dreaming is maintained while reported nightmares actually decline in frequency.[35] Personality patterns typically present in individuals with frequent nightmares include fantasy proneness, psychological absorption, dysphoric daydreaming and ‘thin’ boundaries.[20] Such individuals are more likely to have a creative or artistic focus in their daily lives. Some of these individuals may utilize their dreams and nightmares in highly successful creative careers in writing, acting and film.[36 

Posttraumatic Stress Disorder-associated Nightmares

Frequent nightmares are the most common symptom of PTSD, affecting approximately 25% of individuals who have experienced severe emotional or physical trauma.[37] The nightmares that characterize PTSD are frightening and sometimes stereotypic dreams that can include re-experiencing of the individual’s trauma. Nightmares may be a failure of emotional processing systems that are active during sleep, particularly REM sleep.[22,38] Significant improvement in both sleep onset and maintenance insomnia has been achieved in PTSD patients with the use of both cognitive/behavioral and medication approaches that demonstrably reduce the frequency and distress associated with these disturbing dreams.[39]

Rapid Eye Movement Sleep Behavior Disorder (RBD) and Sleep Paralysis

In patients with RBD, vivid dreams are often ‘acted out.’ Such dream-related behavior can be violent and can result in injury to the victim or bedpartner. In contrast to those who experience sleep terrors, the victim will often recall coherent dream stories that, in a minority of cases, correlate with observed RBD behaviors.[40] RBD events can occur outside the sleep stage for which it is named.[41] During REM sleep associated with sleep paralysis, the inability to perform voluntary movements on waking, with full recall of dreaming, can lead to intense anxiety.

Other Dream-like Parasomnias

Sleep talking (somniloquy), which usually occurs in stage-2 non-REM sleep but which can accompany any stage of sleep, may include embarrassing waking content. Anxiety and panic attacks, also predominately occurring in stage-2, may also include coherent dream content. Sleep related dissociative disorder occurring in individuals with waking dissociative disorders is characterized by re-experiencing of trauma that presents during nighttime awakenings. Nocturnal partial epileptic seizures can include thoughts and hallucinations.[42]


The recent progress that researchers have made in understanding dreams has been incremental, and is not nearly as exciting as the simplified insights, at the time regarded as breakthroughs into the process of consciousness, that were once attributed to dreaming. This recent work indicates that dreaming is a complex cognitive state whether viewed from behavioral, neuroanatomical, neurochemical, pathophysiological or electrophysiological perspectives. Our dreams are what we remember in the morning of the cognition taking place in our CNS during sleep. It is recommended that physicians treating sleep and its disorders be familiar with current knowledge of the science of dreaming. 


Key Points

  • Dreaming is not limited to rapid eye movement (REM) sleep, but rather occurs throughout sleep.
  • Dreaming defined as cognitive narrative, feeling, or awareness of dreaming on awakening occurs in association with many parasomnias.
  • Dreaming is a complex cognitive state whether viewed from behavioral, neuroanatomical, neurochemical, pathophysiological or electrophysiological perspectives.
  • Medications affecting the neurotransmitters/neuromodulators dopamine, nicotine, histamine, gamma-aminobutyric acid (GABA), serotonin, nicotine, and norepinephrine alter dreaming and reported nightmare frequency.


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    • This book providesa state of the art analysis of the highly developed neuroanatomic and neurochemical model for REM sleep.
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  34. Scrima L. Dreaming epiphenomina of narcolepsy, In: Pagel JF, editor. Dreaming and nightmares – sleep medicine clinics, vol. 5. Philadelphia, PA: Saunders; 2010. pp. 261–276.
  35. Pagel JF. The nightmares of sleep apnea: nightmare frequency declines with increasing Apnea Hypopnea Index (AHI). J Clin Sleep Med 2010; 6:69–74.
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Curr Opin Pulm Med. 2012;18(6):574-579

Retrieved from: http://www.medscape.com/viewarticle/772192_2


exercise and adhd…

In ADHD, ADHD Adult, ADHD child/adolescent, Fitness/Health, Neuropsychology, Psychiatry, School Psychology, Special Education on Sunday, 21 October 2012 at 09:43

Exercise May Lead to Better School Performance for Kids with ADHD

ScienceDaily (Oct. 16, 2012)

A few minutes of exercise can help children with attention deficit hyperactivity disorder perform better academically, according to a new study led by a Michigan State University researcher.

The study, published in the current issue of the Journal of Pediatrics, shows for the first time that kids with ADHD can better drown out distractions and focus on a task after a single bout of exercise. Scientists say such “inhibitory control” is the main challenge faced by people with the disorder.

“This provides some very early evidence that exercise might be a tool in our nonpharmaceutical treatment of ADHD,” said Matthew Pontifex, MSU assistant professor of kinesiology, who led the study. “Maybe our first course of action that we would recommend to developmental psychologists would be to increase children’s physical activity.”

While drugs have proven largely effective in treating many of the 2.5 million school-aged American children with ADHD, a growing number of parents and physicians worry about the side effects and costs of medication.

In the study, Pontifex and colleagues asked 40 children aged 8 to 10, half of whom had ADHD, to spend 20 minutes either walking briskly on a treadmill or reading while seated. The children then took a brief reading comprehension and math exam similar to longer standardized tests. They also played a simple computer game in which they had to ignore visual stimuli to quickly determine which direction a cartoon fish was swimming.

The results showed all of the children performed better on both tests after exercising. In the computer game, those with ADHD also were better able to slow down after making an error to avoid repeat mistakes — a particular challenge for those with the disorder.

Pontifex said the findings support calls for more physical activity during the school day. Other researchers have found that children with ADHD are less likely to be physically active or play organized sports. Meanwhile, many schools have cut recess and physical education programs in response to shrinking budgets.

“To date there really isn’t a whole lot of evidence that schools can pull from to justify why these physical education programs should be in existence,” he said. “So what we’re trying to do is target our research to provide that type of evidence.”

Pontifex conducted the study for his doctoral dissertation at the University of Illinois before joining the MSU faculty. His co-investigators included his adviser, kinesiology professor Charles Hillman, and Daniel Picchietti, a pediatrician at the Carle Foundation Hospital in Champaign, Ill. The research was funded by the National Institute of Child Health and Human Development.

Michigan State University (2012, October 16). Exercise may lead to better school performance for kids with ADHD. ScienceDaily. Retrieved October 21, 2012, from http://www.sciencedaily.com­ /releases/2012/10/121016132109.htm

Retrieved from: http://www.sciencedaily.com/releases/2012/10/121016132109.htm

crazily creative…

In Brain imaging, Brain studies, Neuropsychology, Neuroscience on Sunday, 21 October 2012 at 09:38

Link Between Creativity and Mental Illness Confirmed in Large-Scale Swedish Study

ScienceDaily (Oct. 16, 2012)

People in creative professions are treated more often for mental illness than the general population, there being a particularly salient connection between writing and schizophrenia. This according to researchers at Karolinska Institutet, whose large-scale Swedish registry study is the most comprehensive ever in its field.

Last year, the team showed that artists and scientists were more common amongst families where bipolar disorder and schizophrenia is present, compared to the population at large. They subsequently expanded their study to many more psychiatric diagnoses — such as schizoaffective disorder, depression, anxiety syndrome, alcohol abuse, drug abuse, autism, ADHD, anorexia nervosa and suicide — and to include people in outpatient care rather than exclusively hospital patients.

The present study tracked almost 1.2 million patients and their relatives, identified down to second-cousin level. Since all were matched with healthy controls, the study incorporated much of the Swedish population from the most recent decades. All data was anonymized and cannot be linked to any individuals.

The results confirmed those of their previous study, that certain mental illness — bipolar disorder — is more prevalent in the entire group of people with artistic or scientific professions, such as dancers, researchers, photographers and authors. Authors also specifically were more common among most of the other psychiatric diseases (including schizophrenia, depression, anxiety syndrome and substance abuse) and were almost 50 per cent more likely to commit suicide than the general population.

Further, the researchers observed that creative professions were more common in the relatives of patients with schizophrenia, bipolar disorder, anorexia nervosa and, to some extent, autism. According to Simon Kyaga, Consultant in psychiatry and Doctoral Student at the Department of Medical Epidemiology and Biostatistics, the results give cause to reconsider approaches to mental illness.

“If one takes the view that certain phenomena associated with the patient’s illness are beneficial, it opens the way for a new approach to treatment,” he says. “In that case, the doctor and patient must come to an agreement on what is to be treated, and at what cost. In psychiatry and medicine generally there has been a tradition to see the disease in black-and-white terms and to endeavour to treat the patient by removing everything regarded as morbid.”

Simon Kyaga, Mikael Landén, Marcus Boman, Christina M. Hultman, Niklas Långström, Paul Lichtenstein. Mental illness, suicide and creativity: 40-Year prospective total population studyJournal of Psychiatric Research, 2012; DOI: 10.1016/j.jpsychires.2012.09.010

Retrieved from: http://www.sciencedaily.com/releases/2012/10/121016084934.htm

adhd…a longitudinal follow-up

In ADHD, ADHD Adult, ADHD child/adolescent, ADHD stimulant treatment, Brain imaging, Brain studies, Neuropsychology, Neuroscience, Psychiatry, School Psychology on Tuesday, 16 October 2012 at 07:34

Men Diagnosed with ADHD as Children had Worse Outcomes as Adults, Study Says

ScienceDaily (Oct. 15, 2012) — Men who were diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) appeared to have significantly worse educational, occupational, economic and social outcomes in a 33-year, follow-up study that compared them with men without childhood ADHD, according to a report published Online First by Archives of General Psychiatry, a JAMA Network publication.

ADHD has an estimated worldwide prevalence of 5 percent, so the long-term outcome of children with ADHD is a major concern, according to the study background.

Rachel G. Klein, Ph.D., of the Child Study Center at NYU Langone Medical Center in New York, and colleagues report the adult outcome (follow-up at average age of 41 years) of boys who were diagnosed as having ADHD at an average age of 8 years. The study included 135 white men with ADHD in childhood, free of conduct disorder (probands), and a comparison group of 136 men without childhood ADHD.

“On average, probands had 2½ fewer years of schooling than comparison participants … 31.1 percent did not complete high school (vs. 4.4 percent of comparison participants) and hardly any (3.7 percent) had higher degrees (whereas 29.4 percent of comparison participants did). Similarly, probands had significantly lower occupational attainment levels,” the authors note. “Given the probands’ worse educational and occupational attainment, their relatively poorer socioeconomic status at [follow-up at average age of 41 years] is to be expected. Although significantly fewer probands than comparison participants were employed, most were holding jobs (83.7 percent). However, the disparity of $40,000 between the median annual salary of employed probands and comparisons is striking.”

In further comparisons of the two groups, the men who were diagnosed with ADHD in childhood also had more divorces (currently divorced, 9.6 percent vs. 2.9 percent, and ever been divorced 31.1 percent vs. 11.8 percent); and higher rates of ongoing ADHD (22.2 percent vs. 5.1 percent, the authors suspect the comparison participants’ ADHD symptoms might have emerged during adulthood), antisocial personality disorder (ASPD, 16.3 percent vs. 0 percent) and substance use disorders (SUDs, 14.1 percent vs. 5.1 percent), according to the results.

During their lifetime, the men who were diagnosed with ADHD in childhood (the so-called probands) also had significantly more ASPD and SUDs but not mood or anxiety disorders and more psychiatric hospitalizations and incarcerations than comparison participants. And relative to the comparison group, psychiatric disorders with onsets at 21 years of age or older were not significantly elevated in the probands, the study results indicate.

The authors note the design of their study precludes generalizing the results to women and all ethnic and social groups because the probands were white men of average intelligence who were referred to a clinic because of combined-type ADHD.

“The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after 20 years of age. Findings highlight the importance of extended monitoring and treatment of children with ADHD,” the study concludes.

Retrieved from: http://www.sciencedaily.com/releases/2012/10/121015162407.htm



Brain Gray Matter Deficits at 33-Year Follow-up in Adults With Attention-Deficit/Hyperactivity Disorder Established in Childhood

Erika Proal, PhD; Philip T. Reiss, PhD; Rachel G. Klein, PhD; Salvatore Mannuzza, PhD; Kristin Gotimer, MPH; Maria A. Ramos-Olazagasti, PhD; Jason P. Lerch, PhD; Yong He, PhD; Alex Zijdenbos, PhD; Clare Kelly, PhD; Michael P. Milham, MD, PhD; F. Xavier Castellanos, MD

Arch Gen Psychiatry. 2011;68(11):1122-1134. doi:10.1001/archgenpsychiatry.2011.117.


Context  Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood.

Objectives  To test whether adults with combined-type childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis, including persistent vs remitting ADHD.

Design  Cross-sectional analysis embedded in a 33-year prospective follow-up at a mean age of 41.2 years.

Setting  Research outpatient center.

Participants  We recruited probands with ADHD from a cohort of 207 white boys aged 6 to 12 years. Male comparison participants (n = 178) were free of ADHD in childhood. We obtained magnetic resonance images in 59 probands and 80 comparison participants (28.5% and 44.9% of the original samples, respectively).

Main Outcome Measures  Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses.

Results  The cortex was significantly thinner in ADHD probands than in comparison participants in the dorsal attentional network and limbic areas (false discovery rate < 0.05, corrected). In addition, gray matter was significantly decreased in probands in the right caudate, right thalamus, and bilateral cerebellar hemispheres. Probands with persistent ADHD (n = 17) did not differ significantly from those with remitting ADHD (n = 26) (false discovery rate < 0.05). At uncorrected P < .05, individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex, insula, parahippocampus, and prefrontal regions.

Conclusions  Anatomic gray matter reductions are observable in adults with childhood ADHD, regardless of the current diagnosis. The most affected regions underpin top-down control of attention and regulation of emotion and motivation. Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal, cerebellar, and thalamic circuitry.

Retrieved from: http://archpsyc.jamanetwork.com/article.aspx?articleid=1107429

The Unfulfilled Promises of Psychotropics

In Brain studies, Medication, Neuropsychology, Neuroscience, Psychiatry, Psychopharmacology on Sunday, 14 October 2012 at 11:33

The Unfulfilled Promises of Psychotropics

By Richard Kensinger, MSW

I remember thinking over 40 years ago when I began my clinical career, that with the rapid advances made in psychotropic agents, psychotherapy would become a venture of the past. A recent editorial published in Schizophrenia Bulletindispels my myth of becoming unemployed.

Psychopharmacology is in crisis. The data are in, and it is clear that a massive experiment has failed: despite decades of research and billions of dollars invested, not a single mechanistically novel drug has reached the psychiatric market in more than 30 years. Indeed, despite enormous effort, the field has not been able to escape the “me too/me (questionably) better” straightjacket. In recent years, the appreciation of this reality has had profound consequences for innovation in psychopharmacology because nearly every major pharmaceutical company has either reduced greatly or abandoned research and development of mechanistically novel psychiatric drugs. This decision is understandable because pharmaceutical and biotechnology executives see less risky opportunities in other therapeutic areas, cancer and immunology being the current pipeline favorites. Indeed, in retrospect, one can wonder why it took so long for industry to abandon psychiatry therapeutics. So how did we get here and more importantly, what do we need to do to find a way forward?

The discovery of all three major classes of psychiatric drugs, antidepressants, antipsychotics, and anxiolytics, came about on the basis of serendipitous clinical observation. At the time of their discoveries, the mechanisms by which these molecules produce their effects were unknown, and it was only later that antipsychotics were shown to be D2 receptor antagonists, antidepressants monoamine reuptake inhibitors, and anxiolytics GABA receptor modulators. It is interesting and perhaps instructive to consider whether any of these classes of drugs could have been discovered by current drug discovery strategies. For example, what genetic or preclinical data exist that point to the D2 dopamine receptor as a likely target for antipsychotic activity? Presently there are no genetic data that suggest that this receptor is expressed or functions abnormally in psychotic disorders (emphasis added). And without the benefit of the prior clinical validation, it is difficult to see how preclinical data alone would point to the D2 receptor as an interesting potential target for the treatment of psychotic disorders. The same can be said for monoamine transporters with respect to depression where, like psychosis, there are no animal models based on disease pathophysiology and no compelling preclinical data pointing to these as potential targets for antidepressant drugs. This raises a troubling question: if in retrospect the three major classes of currently prescribed psychiatric drugs would likely never have been discovered using current drug discovery strategies, why should we believe that such strategies are likely to bear fruit now or in the future?

Given that there cannot be a coherent biology for syndromes as heterogeneous as schizophrenia, it is not surprising that the field has failed to validate distinct molecular targets for the purpose of developing mechanistically novel therapeutics. Although it has taken our field too long to gain this insight, we seem to be getting there. For example, at the 2011 meeting of the American College of Neuropsychopharmacology, the need for change and the need for new strategies were predominant themes.

In summation the excitement in the past two decades about the “Decades of the Brain” are fading to realism. Our human genome is much more complex than we can imagine. Half of our genes are devoted to brain form and function. The interaction between geneotype and phenotype is also more complex that we realize. Thus, we are approaching this science with more skepticism and realism.


Fibiger HC (2012). Psychiatry, the pharmaceutical industry, and the road to better therapeutics. Schizophrenia bulletin, 38 (4), 649-50 PMID: 22837348

Retrieved from: http://brainblogger.com/2012/10/08/the-unfulfilled-promises-of-psychotropics/


Cannabis and the Adolescent Brain

In Brain studies, Fitness/Health, Neuropsychology, Neuroscience on Sunday, 14 October 2012 at 11:23

Cannabis and the Adolescent Brain

By India Bohanna, PhD

For some time, people have known that using cannabis during adolescence increases the risk of developing cognitive impairment and mental illness (e.g. depression, anxiety or schizophrenia) later in life. Importantly however, the mechanisms responsible for this vulnerability are not well understood. A new study, published in Brain, shows that long-term cannabis use that starts during adolescence damages the neural pathways connecting brain regions, and that this may cause the later development of cognitive and emotional problems.

The authors used diffusion tensor imaging (DTI), a MRI technique that measures water diffusion, to examine the microstructure of white matter in 59 heavy cannabis users, who used cannabis at least twice a month for three years or longer, as well as 33 non-users. In the human brain, white matter pathways are formed by bundles of axons, which carry the neural signals, and myelin, which coat the axons and speeds up signal transfer. These white matter pathways are crucial for normal brain function as they enable disparate regions of the brain to communicate, and act together.

When the authors investigated white matter microstructure in the cannabis users, they found damage in the white matter pathways of the hippocampus, crucial for memory, and the corpus callosum, which connects the brain’s two hemispheres. Both pathways are critical for normal brain function. The authors suggest that impaired connectivity due to damage in these pathways may be the cause of the cognitive impairment and vulnerability to schizophrenia, depression and anxiety seen in long-term users.

The authors also show an inverse relationship between the amount of white matter damage and the age of first use. That is, participants who started using cannabis younger had more white matter damage and showed poorer brain connectivity. Adolescence is a critical period in the development of white matter in the brain, when the neural connections we rely on in adulthood are being finally formed. The authors point out that white matter cells have cannabinoid receptors (those susceptible to cannabis) during adolescence, which disappear as the brain matures. This new study demonstrates a mechanism that may help explain how cannabis use in adolescence causes long-term changes in brain function. The cannabis users in the study had significantly higher levels of depression and anxiety compared to the non-users.

This important new study suggests that young people’s brains are at risk of white matter injury due to cannabis, and that cannabis exposure during adolescence may permanently damage white matter development. Future research must address the question; can white matter pathways and connectivity recover when a person quits using cannabis?


Zalesky A, Solowij N, Yücel M, Lubman DI, Takagi M, Harding IH, Lorenzetti V, Wang R, Searle K, Pantelis C, & Seal M (2012). Effect of long-term cannabis use on axonal fibre connectivity. Brain : a journal of neurology, 135 (Pt 7), 2245-55 PMID: 22669080

Retrieved from: http://brainblogger.com/2012/08/18/cannabis-and-the-adolescent-brain/

Smoking and the Adolescent Brain

In Fitness/Health, Neuropsychology, Neuroscience on Sunday, 14 October 2012 at 11:18

Smoking and Adolescent Brain Development

By Shefali Sabharanjak, PhD

When it comes to substance abuse like smoking or abuse of intoxicating drugs, it is very difficult to determine what a “safe” limit of exposure is.  Quite often, the initial exposure to mood altering substances like nicotine occurs during the teenage years. The period ofadolescence is marked by a tendency towards risk-taking behavior which often results in ‘experimental’ exposure to psychedelic substances. Adolescents who tend to flirt with danger in this fashion are often convinced that a small trial will not actually have lasting damaging effects. However, research on the development of prefrontal cortex in similarly age-matched animals says otherwise.

The prefrontal cortex in teenagers is in a state of growth and development. Contrary to established notions, brain development continues well into the teenage years and changes in synapses (connections between brain cells that facilitate the transmission of chemical messengers between cells) occur well into adolescence.  Research on adolescent mice and rats shows that exposure to nicotine during this period has long-lasting effects. For starters, nicotine is known to be able to excite neurons bearing nicotinic acetylcholine receptors. In the prefrontal cortex, nicotine has been shown to induce greater expression of a specific subset of nicotinic acetylcholine receptors, by 34%.  In the normal course of development, the number of acetylcholine receptors declines in these cells. This phenomenon is specific to the period of adolescence since a similar increase in the number of receptors is not seen when the initial exposure to nicotine occurs in adulthood, in these animals. Research has also shown that exposure to nicotine in early adolescence enhances the nicotinic ‘reward’ feeling during adulthood. It is therefore surmised that early exposure to smoking is likely to set the stage for long-term addiction and perhaps it also explains why addiction to nicotine is so prevalent, worldwide.

One might argue that since the teenage years are a short period in the life-span of a person, occasional exposure to nicotine is not likely to leave lasting damage. Here’s the catch. Exposure to nicotine also changes the pattern of synaptic connectivity between neurons in the prefrontal cortex.  The ability of neurons to establish new synaptic connections and develop new firing patterns in response to different stimuli is also known as “synaptic plasticity”. Neuroscientists have shown that all “learning” as well as  information analysis and assimilation in the brain is a net result of the pattern of exchange of neurotransmitter molecules (also referred to as pattern of ‘firing’) between neurons which respond to training stimuli. So, the more you learn, the better you get at learning by stimulating your neurons to make new synaptic connections. However, exposure to nicotine in early adolescence, changes the pattern of firing of neurons in the prefrontal cortex. Now this change reduces the capability of neurons in the prefrontal cortex to make new synaptic connections. Therefore exposure to psychedelic and addictive substances like nicotine results in reduced synaptic plasticity and has a negative impact on cognitive processes in adult life.

All these significant changes take place in early adolescence and perhaps parental guidance may play a huge role in preventing nicotine addiction and associated cognitive deficits.


Adriani W, Macrì S, Pacifici R, & Laviola G (2002). Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 27 (2), 212-24 PMID: 12093595

Counotte DS, Goriounova NA, Moretti M, Smoluch MT, Irth H, Clementi F, Schoffelmeer AN, Mansvelder HD, Smit AB, Gotti C, & Spijker S (2012). Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 26 (5), 1810-20 PMID: 22308197

Goriounova NA, & Mansvelder HD (2012). Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood. Frontiers in synaptic neuroscience, 4 PMID: 22876231

Goriounova NA, & Mansvelder HD (2012). Nicotine exposure during adolescence leads to short- and long-term changes in spike timing-dependent plasticity in rat prefrontal cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (31), 10484-93 PMID: 22855798

Kawai HD, Kang HA, & Metherate R (2011). Heightened nicotinic regulation of auditory cortex during adolescence. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (40), 14367-77 PMID: 21976522

Kota D, Robinson SE, & Imad Damaj M (2009). Enhanced nicotine reward in adulthood after exposure to nicotine during early adolescence in mice. Biochemical pharmacology, 78 (7), 873-9 PMID: 19576867

Retrieved from: http://brainblogger.com/2012/10/14/smoking-and-adolescent-brain-development/?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+GNIFBrainBlogger+%28Brain+Blogger%29


more awesomeness in neuroscience…

In Education, Neurogenesis, Neuropsychology, Neuroscience, School Psychology on Saturday, 13 October 2012 at 09:30

Brain Scans Can Detect Children’s Reading Ability


Stanford researchers say that brain scans can help detect whether or not a child will develop reading-related problems in the future, a discovery that opens up possibility of intervention programs for helping children improve their reading ability.  In a study, conducted over a period of three years, researchers at Stanford University assessed children’s reading skills with the help of standardized tests. They observed and analyzed the participants’ brain scans taken during the study.

Researchers found that in each of the 39 children, the rate of development in the white matter region accurately predicted the child’s score on a reading test. The white matter regions of the brain are associated with reading; the rate of development in the brain region is measured by fractional anisotropy, or FA.

Further, children who displayed above-average reading skills had FA in two regions, the left hemisphere arcuate fasciculus and the left hemisphere inferior longitudinal fasciculus. Interestingly, in children who develop good reading skills, the initial FA was lower but increased over time. In children that had lower reading abilities, the FA was higher initially but declined afterwards.

According to researchers, a child’s ability to read at seven years of age can predict hisor her reading ability at 17 years of age. But, detecting if the child has problems with reading can be a challenge. “By the time kids reach elementary school, we’re not great at finding ways of helping them catch up,” said Jason D. Yeatman, a doctoral candidate in psychology at Stanford and the lead author on the study.

The great news is the study could one day lead to an early warning system for struggling students and this could help children improve their reading ability as the brain is young and is still developing.

“Once we have an accurate model relating the maturation of the brain’s reading circuitry to children’s acquisition of reading skills, and once we understand which factors are beneficial, I really think it will be possible to develop early intervention protocols for children who are poor readers, and tailor individualized lesson plans to emphasize good development. Over the next five to 10 years, that’s what we’re really hoping to do,” Yeatman said.

The study was published in the Proceedings of the National Academy of Sciences.

Retrieved from: http://www.medicaldaily.com/articles/12666/20121012/brain-scans-detect-childrens-reading-ability.htm#go5H3ZzSAe1jtK0g.99

Development of white matter and reading skills

PNAS Plus – Biological Sciences – Psychological and Cognitive Sciences

Jason D. Yeatman, Robert F. Dougherty, Michal Ben-Shachar, and Brian A. Wandell

White matter tissue properties are highly correlated with reading proficiency; we would like to have a model that relates the dynamics of an individual’s white matter development to their acquisition of skilled reading. The development of cerebral white matter involves multiple biological processes, and the balance between these processes differs between individuals. Cross-sectional measures of white matter mask the interplay between these processes and their connection to an individual’s cognitive development. Hence, we performed a longitudinal study to measure white-matter development (diffusion-weighted imaging) and reading development (behavioral testing) in individual children (age 7–15 y). The pattern of white-matter development differed significantly among children. In the left arcuate and left inferior longitudinal fasciculus, children with above-average reading skills initially had low fractional anisotropy (FA) that increased over the 3-y period, whereas children with below-average reading skills had higher initial FA that declined over time. We describe a dual-process model of white matter development comprising biological processes with opposing effects on FA, such as axonal myelination and pruning, to explain the pattern of results.

PNAS Plus: Development of white matter and reading skillsPNAS 2012 ; published ahead of print October 8, 2012,doi:10.1073/pnas.1206792109

Retrieved from: http://www.pnas.org/search?fulltext=reading&go.x=0&go.y=0&go=GO&submit=yes



ADHD…a “made up” disorder???

In ADHD, ADHD Adult, ADHD child/adolescent, ADHD stimulant treatment, Medication, Neuropsychology, Psychiatry, Psychopharmacology, School Psychology on Thursday, 11 October 2012 at 10:37

while i do think adhd is the “diagnosis of the day” and it may be over-diagnosed, i DO NOT agree that it is a “made up”  disorder or “an excuse.”  you only have to look at the latest studies that compare treated and untreated brains of those diagnosed with adhd to see that there are real neurological and neuroanatomical deficits that can arise if adhd is left untreated (for one example, see: Adult ADHD: New Findings in Neurobiology and Genetics ; Scott H. Kollins, Ph.D.  http://www.medscape.org/viewarticle/765528).  

if you think you or someone you know has adhd, the following lists suggestions to make sure you receive a valid diagnosis and what to help to facilitate that*:

A good evaluation may consist of many of the following:

  • Collection of rating scales and referral information before or during the evaluation  
  • An interview with the student and parents
  • A review of previous records that may document impairments (i.e. problems in school, socially, or at home that you believe can be attributed to ADHD.  A good doctor knows exactly what questions to ask.
  • A general medical examination when medication might be part of treatment or coexisting medical conditions need to be evaluated (if the physician hasn’t already done this). 

 What to take along to facilitate these steps:  

  • Any records from schools you.your child attended and any other documentation of problems that could be related to ADHD or another disorder 
  • A list of family members with mental health known disorders
  • A description of impairments during childhood (i.e. elementary school), as well as more recent ones (i.e. middle school).  This can be done via SST notes, progress reports, psychological evaluations, IEP’s, etc.

*adapted from: Barkley, Russell A. (2011-04-04). Taking Charge of Adult ADHD (Kindle Locations 464-483). Guilford Press. Kindle Edition.

Attention Disorder or Not, Pills to Help in School

Alan Schwarz

CANTON, Ga. — When Dr. Michael Anderson hears about his low-income patients struggling in elementary school, he usually gives them a taste of some powerful medicine: Adderall.

The pills boost focus and impulse control in children with attention deficit hyperactivity disorder. Although A.D.H.D is the diagnosis Dr. Anderson makes, he calls the disorder “made up” and “an excuse” to prescribe the pills to treat what he considers the children’s true ill — poor academic performance in inadequate schools.

“I don’t have a whole lot of choice,” said Dr. Anderson, a pediatrician for many poor families in Cherokee County, north of Atlanta. “We’ve decided as a society that it’s too expensive to modify the kid’s environment. So we have to modify the kid.”

Dr. Anderson is one of the more outspoken proponents of an idea that is gaining interest among some physicians. They are prescribing stimulants to struggling students in schools starved of extra money — not to treat A.D.H.D., necessarily, but to boost their academic performance.

It is not yet clear whether Dr. Anderson is representative of a widening trend. But some experts note that as wealthy students abuse stimulants to raise already-good grades in colleges and high schools, the medications are being used on low-income elementary school children with faltering grades and parents eager to see them succeed.

“We as a society have been unwilling to invest in very effective nonpharmaceutical interventions for these children and their families,” said Dr. Ramesh Raghavan, a child mental-health services researcher at Washington University in St. Louis and an expert in prescription drug use among low-income children. “We are effectively forcing local community psychiatrists to use the only tool at their disposal, which is psychotropic medications.”

Dr. Nancy Rappaport, a child psychiatrist in Cambridge, Mass., who works primarily with lower-income children and their schools, added: “We are seeing this more and more. We are using a chemical straitjacket instead of doing things that are just as important to also do, sometimes more.”

Dr. Anderson’s instinct, he said, is that of a “social justice thinker” who is “evening the scales a little bit.” He said that the children he sees with academic problems are essentially “mismatched with their environment” — square pegs chafing the round holes of public education. Because their families can rarely afford behavior-based therapies like tutoring and family counseling, he said, medication becomes the most reliable and pragmatic way to redirect the student toward success.

“People who are getting A’s and B’s, I won’t give it to them,” he said. For some parents the pills provide great relief. Jacqueline Williams said she can’t thank Dr. Anderson enough for diagnosing A.D.H.D. in her children — Eric, 15; Chekiara, 14; and Shamya, 11 — and prescribing Concerta, a long-acting stimulant, for them all. She said each was having trouble listening to instructions and concentrating on schoolwork.

“My kids don’t want to take it, but I told them, ‘These are your grades when you’re taking it, this is when you don’t,’ and they understood,” Ms. Williams said, noting thatMedicaid covers almost every penny of her doctor and prescription costs.

Some experts see little harm in a responsible physician using A.D.H.D. medications to help a struggling student. Others — even among the many like Dr. Rappaport who praise the use of stimulants as treatment for classic A.D.H.D. — fear that doctors are exposing children to unwarranted physical and psychological risks. Reported side effects of the drugs have included growth suppression, increased blood pressure and, in rare cases, psychotic episodes.

The disorder, which is characterized by severe inattention and impulsivity, is an increasingly common psychiatric diagnosis among American youth: about 9.5 percent of Americans ages 4 to 17 were judged to have it in 2007, or about 5.4 million children, according to the Centers for Disease Control and Prevention.

The reported prevalence of the disorder has risen steadily for more than a decade, with some doctors gratified by its widening recognition but others fearful that the diagnosis, and the drugs to treat it, are handed out too loosely and at the exclusion of nonpharmaceutical therapies.

The Drug Enforcement Administration classifies these medications as Schedule II Controlled Substances because they are particularly addictive. Long-term effects of extended use are not well understood, said many medical experts. Some of them worry that children can become dependent on the medication well into adulthood, long after any A.D.H.D. symptoms can dissipate.

According to guidelines published last year by the American Academy of Pediatrics, physicians should use one of several behavior rating scales, some of which feature dozens of categories, to make sure that a child not only fits criteria for A.D.H.D., but also has no related condition like dyslexia or oppositional defiant disorder, in which intense anger is directed toward authority figures. However, a 2010 study in the Journal of Attention Disorders suggested that at least 20 percent of doctors said they did not follow this protocol when making their A.D.H.D. diagnoses, with many of them following personal instinct.

On the Rocafort family’s kitchen shelf in Ball Ground, Ga., next to the peanut butter and chicken broth, sits a wire basket brimming with bottles of the children’s medications, prescribed by Dr. Anderson: Adderall for Alexis, 12; and Ethan, 9; Risperdal (an antipsychotic for mood stabilization) for Quintn and Perry, both 11; and Clonidine (a sleep aid to counteract the other medications) for all four, taken nightly.

Quintn began taking Adderall for A.D.H.D. about five years ago, when his disruptive school behavior led to calls home and in-school suspensions. He immediately settled down and became a more earnest, attentive student — a little bit more like Perry, who also took Adderall for his A.D.H.D.

When puberty’s chemical maelstrom began at about 10, though, Quintn got into fights at school because, he said, other children were insulting his mother. The problem was, they were not; Quintn was seeing people and hearing voices that were not there, a rare but recognized side effect of Adderall. After Quintn admitted to being suicidal, Dr. Anderson prescribed a week in a local psychiatric hospital, and a switch to Risperdal.

While telling this story, the Rocaforts called Quintn into the kitchen and asked him to describe why he had been given Adderall.

“To help me focus on my school work, my homework, listening to Mom and Dad, and not doing what I used to do to my teachers, to make them mad,” he said. He described the week in the hospital and the effects of Risperdal: “If I don’t take my medicine I’d be having attitudes. I’d be disrespecting my parents. I wouldn’t be like this.”

Despite Quintn’s experience with Adderall, the Rocaforts decided to use it with their 12-year-old daughter, Alexis, and 9-year-old son, Ethan. These children don’t have A.D.H.D., their parents said. The Adderall is merely to help their grades, and because Alexis was, in her father’s words, “a little blah.”

”We’ve seen both sides of the spectrum: we’ve seen positive, we’ve seen negative,” the father, Rocky Rocafort, said. Acknowledging that Alexis’s use of Adderall is “cosmetic,” he added, “If they’re feeling positive, happy, socializing more, and it’s helping them, why wouldn’t you? Why not?”

Dr. William Graf, a pediatrician and child neurologist who serves many poor families in New Haven, said that a family should be able to choose for itself whether Adderall can benefit its non-A.D.H.D. child, and that a physician can ethically prescribe a trial as long as side effects are closely monitored. He expressed concern, however, that the rising use of stimulants in this manner can threaten what he called “the authenticity of development.”

“These children are still in the developmental phase, and we still don’t know how these drugs biologically affect the developing brain,” he said. “There’s an obligation for parents, doctors and teachers to respect the authenticity issue, and I’m not sure that’s always happening.”

Dr. Anderson said that every child he treats with A.D.H.D. medication has met qualifications. But he also railed against those criteria, saying they were codified only to “make something completely subjective look objective.” He added that teacher reports almost invariably come back as citing the behaviors that would warrant a diagnosis, a decision he called more economic than medical.

“The school said if they had other ideas they would,” Dr. Anderson said. “But the other ideas cost money and resources compared to meds.”

Dr. Anderson cited William G. Hasty Elementary School here in Canton as one school he deals with often. Izell McGruder, the school’s principal, did not respond to several messages seeking comment.

Several educators contacted for this article considered the subject of A.D.H.D. so controversial — the diagnosis was misused at times, they said, but for many children it is a serious learning disability — that they declined to comment. The superintendent of one major school district in California, who spoke on the condition of anonymity, noted that diagnosis rates of A.D.H.D. have risen as sharply as school funding has declined.

“It’s scary to think that this is what we’ve come to; how not funding public education to meet the needs of all kids has led to this,” said the superintendent, referring to the use of stimulants in children without classic A.D.H.D. “I don’t know, but it could be happening right here. Maybe not as knowingly, but it could be a consequence of a doctor who sees a kid failing in overcrowded classes with 42 other kids and the frustrated parents asking what they can do. The doctor says, ‘Maybe it’s A.D.H.D., let’s give this a try.’ ”

When told that the Rocaforts insist that their two children on Adderall do not have A.D.H.D. and never did, Dr. Anderson said he was surprised. He consulted their charts and found the parent questionnaire. Every category, which assessed the severity of behaviors associated with A.D.H.D., received a five out of five except one, which was a four.

“This is my whole angst about the thing,” Dr. Anderson said. “We put a label on something that isn’t binary — you have it or you don’t. We won’t just say that there is a student who has problems in school, problems at home, and probably, according to the doctor with agreement of the parents, will try medical treatment.”

He added, “We might not know the long-term effects, but we do know the short-term costs of school failure, which are real. I am looking to the individual person and where they are right now. I am the doctor for the patient, not for society.

Retrieved from: http://www.nytimes.com/2012/10/09/health/attention-disorder-or-not-children-prescribed-pills-to-help-in-school.html?pagewanted=all&pagewanted=print

The Energetic Brain…a great reference for ADHD

In ADHD, ADHD Adult, ADHD child/adolescent, ADHD stimulant treatment, Medication, Neuropsychology, Psychiatry, Psychopharmacology, School Psychology on Sunday, 7 October 2012 at 09:27

everything you ever wanted to know about adhd. a wonderful reference!


Information regarding the upcoming DSM V

In Neuropsychology, Psychiatry, School Psychology on Wednesday, 26 September 2012 at 08:00

DSM-5: Finding a Middle Ground

Nassir Ghaemi, MD

DSM-5: Validity vs Reliability

This year’s American Psychiatric Association (APA) annual meeting was probably the last before the publication of theDiagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), scheduled for May of next year. Hence, there was a sense of tense uncertainty in the many sessions addressing potential DSM-5 revisions.

DSM-5 Task Force Vice Chair Darrel Regier headed a symposium reviewing results of field trials on the reliability of proposed DSM-5 criteria. The trials were meant to assess whether clinicians can use the proposed criteria consistently and provided kappa values for the individual proposals.

Kappa values reflect the agreement in a rating by 2 different persons, after correction for chance agreement. From a statistical perspective, kappa values greater than 0.5 are generally considered good. As an example, 70% agreement between raters translates to a kappa value of 0.4.

Results of the field trials showed good agreement for such disorders as major neurocognitive disorder, autism spectrum disorders, and post-traumatic stress disorder, with kappa values of 0.78, 0.69, and 0.67, respectively. However, poor kappa values, in the range of 0.20-0.40, were reported for commonly diagnosed conditions, such as generalized anxiety disorder and major depressive disorder. All of the observed kappa values in the DSM-5 field trials translate to agreement between clinicians of around 50%.

Is this good or bad? A recent editorial[1] by DSM-5 leaders makes comparisons with other medical settings, and the claim is that most medical diagnoses involve diagnostic kappa values similar to those in the DSM-5 field trials. I spoke with prominent psychiatrists at this year’s meeting who were involved in some of these DSM studies and discussions; they expressed unhappiness with the kappa values in DSM-5 field trials, and some pointed out that kappa values in the DSM-III were higher.

So, the reliability of DSM-5 criteria seems to have declined compared to DSM-III. Is this a problem? It might be, but it might not be.

Reliability only means that we agree. It doesn’t mean that we agree on what is right. Validity is a separate issue. It could be that criteria are changed so that they are more valid — that is, actually true — but this could increase unreliability; raters might have to use, for instance, some criteria that are less objective and hence less replicable.

We will see. DSM-5 might be more valid but less reliable than DSM-IV and DSM-III. If so, that’s progress, in a way.

It is also important to think about other medical studies with low reliability. We should be careful about criticizing certain diagnoses, such as bipolar disorder (as some have[2]), without an awareness that this is the case for almost all our diagnoses. The problem of reliability is a general one, not a problem about claimed “overdiagnosis” of some conditions.

In my view, it is definitely time for a new edition of DSM; we can’t pretend that something written almost 2 decades ago is anywhere near up to date, with a generation of new research. Some of the proposed changes in DSM-5 — for example, the inclusion of antidepressant-induced mania as part of bipolar disorder; the inclusion of dimensions for axis II personality conditions; and the removal of nosologically nonspecific axis II diagnoses, such as “histrionic” personality — are consistent with an update based on convincing new research. But other changes, such as the wish to discourage the diagnosis of childhood bipolar disorder by making up a new category based on limited data (temper dysregulation disorder), merely repeat the mistakes of DSM-IV. Making up diagnoses because we don’t like others is not a scientifically sound way to revise a profession’s diagnostic system, and it won’t serve us well for the next 20 years.

But DSM-IV Has Limitations, Too

Also at this year’s APA meeting, Steven Hyman, a psychiatrist and neurobiology researcher who is former head of the National Institute of Mental Health, gave a plenary lecture on DSM-5 that was refreshingly honest in its appreciation of the limitations that the DSM-IV has placed on research. Rewinding to DSM-III, from the 1980s, he made the point that although that edition was a major advance, it is now out of date, and that DSM-IV, which merely continued the basic DSM-III structure, needs major changes. “The DSM-III was a brilliant document that could not have foreseen the science. It’s time to move on scientifically,” said Hyman.

Hyman noted that DSM-III actually hinders science. Researchers have difficulty getting funding from the National Institutes of Health or publishing papers that go outside DSM criteria: “For example, it was very hard to get a grant to test the hypothesis that maybe the apparent comorbidity of multiple anxiety disorder and mood disorders was just that there was a single underlying process or single disorder that got expressed with different symptom complexes in different times in life.”

There was a name for that condition — neurotic depression — and Sir Martin Roth, the great British psychopathologist, warned repeatedly in the 1970s and 1980s that it would be a mistake for DSM-III to remove it. DSM-III made that mistake, and the field has since acted like it would be a sin to study the matter any further.

There are many examples of this ilk in DSM-III and DSM-IV. Some who are upset with proposed changes in DSM-5 are diagnostic conservatives who seem to think that all our questions were answered in 1980 and 1994.

Dr. Hyman has been influential in designing the new Research Domain Criteria (RDOC), an attempt to create a DSM for research that begins with biological, rather than clinical, terms. I agree with the need for a DSM for research, but I don’t think our biological knowledge is advanced enough yet — despite all the advances that have been made — to build a diagnostic system from them, even for research purposes.

I think we should have a new DSM just for research: a system of Research Diagnostic Criteria (RDC), like what was created in the 1970s that led to DSM-III to begin with. I’ve started that process with my colleagues in the world of bipolar disorder research. We will publish a new RDC for bipolar disorder within the coming year — before DSM-5, I hope. If we do so, I hope that colleagues in other specialties in psychiatry will produce similar RDCs.

With these new publications, psychiatry may then be in a position for real advance. We will then have 3 nosologies, all complementary to each other and able to improve the others:

  1. DSM-5: a nosology based on a mix of research, economic concerns, social preferences, and professional consensus that is used for basic practice, insurance reimbursement, and short-term consensus.
  2. RDOC: a nosology based solely on biological research that is used for research.
  3. RDC: a nosology based solely on clinical research that is used for research.

In summary, DSM-5 is on its way, and May 2013 is as good a date as any for its publication. In some places, it will be a much-needed advance over the now-outdated DSM-IV. But in other places, it keeps old categories that are not as well proven as they should be, and it even adds a few new categories that are mainly based on professional, economic, and social concerns rather than on sufficient scientific evidence.


  1. Kraemer HC, Kupfer DJ, Clarke DE, Narrow WE, Regier DA. DSM-5: how reliable is reliable enough? Am J Psychiatry. 2012;169:13-15. http://ajp.psychiatryonline.org/article.aspx?articleid=181221 Accessed May 15, 2012.
  2. Zimmerman M, Ruggero CJ, Chelminski I, Young D. Is bipolar disorder overdiagnosed? J Clin Psychiatry. 2008;69:935-940.

Retrieved from: http://www.medscape.com/viewarticle/764740?src=ptalk

Noninvasive Prenatal Diagnosis: Can Ethics and Science Meet?

In Genes, Genomic Medicine, Neuropsychology, Neuroscience on Wednesday, 26 September 2012 at 07:30

posting as an addition to my recent post on genomic medicine.  the growing field and research in genomic medicine raises some interesting ethical issues.

Noninvasive Prenatal Diagnosis: Can Ethics and Science Meet?

Elizabeth H. Dorfman; Mildred Cho, PhD

Editor’s Note:
Technological advances have enabled researchers to sequence an entire fetal genome noninvasively by extracting cell-free fetal DNA from maternal plasma.[1,2] This use of noninvasive prenatal diagnosis (NIPD) shifts the focus away from screening for known or suspected anomalies and inherited conditions to potentially discovering a wide array of information about the fetus that patients and clinicians might not be prepared to address.

On behalf of Medscape, Elizabeth H. Dorfman, a graduate student at the University of Washington Institute for Public Health Genetics, Seattle, Washington, interviewed Mildred Cho, PhD, Professor at the Stanford Center for Biomedical Ethics, Stanford, California, about the ethical and social implications of NIPD and how advances in these techniques might affect clinical practice.

Ms. Dorfman: Let’s start with a few background questions to set the stage. Can you briefly describe the technique behind NIPD using cell-free fetal DNA?

Dr. Cho: NIPD allows prenatal testing to be done from a sample of maternal blood instead of having to take a sample through invasive techniques, such as amniocentesis or chorionic villus sampling. There are a lot of different ways of analyzing fetal DNA in maternal serum; this technology, which is more recently developed, enables one to look at fragments of cell-free fetal DNA as opposed to fetal cells in maternal blood.

Ms. Dorfman: In regard to the timing of testing, risk to the fetus or the pregnancy, or potential for incidental findings — are they substantively different for NIPD compared with existing tests, or are they similar?

Dr. Cho: NIPD could potentially be used earlier in gestation, so that would give people more time to think about what to do with the results. Right now, I don’t think it’s being used very early because the ability to get enough DNA in the sample hasn’t been worked out fully, but that is the hope. Obviously, because it’s noninvasive, that makes a big difference to the person who is giving the sample: Not only is it not uncomfortable or painful, but there is virtually no risk to the fetus from taking the sample.

Ms. Dorfman: A team at the University of Washington recently announced that they had used noninvasive cell-free fetal DNA methods to sequence the entire genome of a developing fetus.[1] Could you go into a little bit of detail about how this changes the scope of NIPD?

Dr. Cho: Currently, fetal testing is done either to screen for one of a small number of conditions, or as follow-up to a prior screening, such as a genetic screening or fetal ultrasonography. In these cases, the fetal diagnostic test will be used to focus on any conditions or anomalies that turned up positive in the prior screen, or to detect a condition that is of particular concern that may have been identified through a family history. So, diagnostic testing will be just that: diagnostic, trying to come up with a genetic cause for an observed or suspected anomaly.

When or if it becomes possible to do whole-genome analysis in a clinical setting routinely, it will open up the possibility that people can get information about the fetus that is well beyond a handful of known fetal conditions, such as a trisomy. This raises the concern that people will be faced with a huge amount of information about which there might be a lot of uncertainty and will have very little time to consider what to do with the information.

Thinking even further into the future, one of the concerns is that it could potentially change the way people think about pregnancy because it might be perceived that they have a lot of choices to make about what kind of children they want to have. Moving from a limited set of conditions to potentially any kind of human trait that has a major genetic component could really change the way people think about pregnancy and prenatal testing.

Ms. Dorfman: How does this potentially expanded capability reconcile with current practice guidelines and policy statements related to genetic testing in children? For example, the American Academy of Pediatrics Committee on Genetics’ recommendations on ethical issues with genetic testing in pediatrics,[3] or the National Society of Genetic Counselors’ position statements on prenatal and childhood testing for adult-onset disorders.[4]

Dr. Cho: There is going to have to be some further thought about how this kind of fetal testing might be used by clinicians. The current guidelines don’t really speak to whether there are professional limits on what clinicians will and will not use genetic testing for, so the clinical communities will have to ask themselves whether there are any genetic traits for which they won’t offer testing, or whether there are any limits on information that they will provide to patients.

Ms. Dorfman: As a follow-up to that, the editor’s summary of the University of Washington study that was published in Science Translational Medicine [1] stated, “An ideal prenatal genetic diagnostic would noninvasively screen for all Mendelian disorders early in pregnancy.” I was wondering whether you agreed with or had any comments about that statement.

Dr. Cho: We have to think about what “ideal” means to different people. We can currently test for a lot of mendelian conditions, and yet a lot of people don’t opt to get those tests. For a lot of people, that kind of information might be unwanted; some of it may be the kind of information that won’t have any bearing on how people treat their pregnancies, or it may not be relevant until after the child is born. I think that’s something that can be debated, whether that’s an ideal situation or not.

Ms. Dorfman: NIPD requires a blood sample from the pregnant woman, and as you have described, carries no risk for miscarriage or direct fetal harm. Of note, this has raised concerns about inadequate informed consent, and I was hoping that you can comment on where this concern came from.

Dr. Cho: People who are already familiar with prenatal screening tests that analyze maternal serum already know that sometimes, women may not realize that one of the blood samples taken during pregnancy was not used to check their blood glucose, but was actually a prenatal screening test. So I think the concern is that if there isn’t a specific and unique procedure that is part of the prenatal testing process, it could go almost unnoticed until the results come back — and then be a shock to people who get the results. They might not understand the implications of this type of testing.

Ms. Dorfman: Is there consensus about the information and risks that should be disclosed in the informed consent process before NIPD?

Dr. Cho: I don’t think there is consensus on how to deal with information that should be disclosed in almost any clinical situation, and no, I don’t think that there is consensus for how to deal with genomic results and NIPD.

Ms. Dorfman: What risks do you think should be disclosed before testing?

Dr. Cho: People should understand that a prenatal test is being done and that the information they might receive from that test could be very broad and potentially have a major impact on decision-making. And if they have a choice to not get all that information, they should understand that as well.

The consent process should note the risk for getting information that the person might not want, and also that the information might affect family members as well, who may not be interested in getting genomic information.

Ms. Dorfman: Noninvasive testing using cell-free fetal DNA can be used to determine fetal gender as early as 7 weeks’ gestation. Is there any reason to think that this will promote prenatal sex selection in regions where this has not been a problem or exacerbate the practice in regions where this is already a concern?

Ms. Cho: There might be reason to be concerned about the use of cell-free fetal DNA testing for sex selection, especially in areas where gender imbalance is already widespread. Even if there are laws against sex selection, it would be relatively easy to get a blood sample and also relatively easy to send it out of the country, and to get a result back.

It’s something to be aware of and keep tabs on. Companies that offer testing will have to think about how they’re going to determine whether the samples are being used for things that are actually illegal in other countries; it may be their obligation to ensure that they’re not contributing to illegal behavior.

Ms. Dorfman: The American College of Obstetrics and Gynecology has published a position statement that this new technology should not be used for the purposes of sex selection.[5] Do you have any recommendations on what, if anything, should be done proactively to prevent that from becoming an issue in such countries as the United States, where we don’t see this as an issue but where we also don’t have laws banning it?

Dr. Cho: There is a professional stance against sex testing in the United States. But in places where sex testing is not necessarily against professional guidelines or is illegal, there needs to be more thought about what responsibility the testing companies have and what practical measures laboratories can take to ensure that they’re not potentially violating the law.

Ms. Dorfman: There is significant interest in whether and when to return genetic results to patients. How does this take shape in NIPD?

Dr. Cho: This question of returning results of genomic findings may be even more important in prenatal testing than in other clinical situations. In prenatal settings, patients typically have very broad autonomy to make decisions about what kind of information they seek and about what kind of information they have access to. It’s a little different from returning results in, say, adult medicine where you could argue that genomic results shouldn’t be treated any differently from other kinds of medical testing. But in the prenatal setting, there is usually such a premium put on autonomy of the patient to make decisions about her pregnancy that it puts the issue of returning results in a bit of a different light.

Ms. Dorfman: Noninvasive methods that require both a maternal and a paternal sample to determine which of the DNA segments are from the fetus could introduce additional opportunities for incidental findings. Could you comment on that?

Dr. Cho: I agree; when you’re getting samples from the mother and the father, you definitely have a much greater potential for incidental findings. It should be part of the consent process and their understanding of what kind of results they may potentially get back.

Ms. Dorfman: What efforts are currently under way to characterize how NIPD is affecting clinical practice and reproductive decision-making, if any?

Dr. Cho: Some people are studying the clinical implementation of NIPD, which is currently limited to aneuploidy detection. I don’t know that it’s being studied broadly for applications other than aneuploidy at this point, but I imagine that will happen in the near future.

A side issue that might become influential in the application of cell-free fetal DNA research to clinical practice is the question of intellectual property and whether patents for cell-free fetal DNA testing might affect how clinicians can or cannot use the test. The ethical side of this is how or whether intellectual property policy should be allowed to dictate how clinical tests are or are not available to clinicians and patients.

Ms. Dorfman: Looking ahead, how do you think can we best maximize the benefits of cell-free fetal DNA testing capabilities while minimizing the potential harm? Are there regulations or policies that can be implemented that you think would yield a favorable balance of risks and benefits?

Dr. Cho: That’s a good question, but I don’t have a very good answer. Some of the concerns about potentially eugenic uses of cell-free fetal DNA in a prenatal setting are very difficult to address at the policy level, and we haven’t done a very good job of that so far with other kinds of prenatal testing. A lot will depend on such things as informed consent, which has not proven very effective right now for other types of prenatal testing, so it is likely going to be a difficult problem to tackle.

The US Food and Drug Administration might be more willing to regulate this kind of genetic testing than other kinds of genetic testing simply because the nature of the decisions made in the prenatal setting are so much more ethically fraught and important. More specific scrutiny of prenatal genetic testing, putting into play some kind of mechanism for quality control, quality assessment, and accuracy at an analytic level would at least help to minimize some of the risks from having inaccurate results.

But the large social and ethical issues are going to be very difficult to address through policy, and clinicians are going to have a hard time dealing with them. Up to this point, we’ve been very reluctant to interfere with prenatal decision-making. Much of this will probably end up being left to public education efforts, which may be of limited effectiveness.


  1. Kitzman JO, Snyder MW, Ventura M, et al. Noninvasive whole-genome sequencing of a human fetus. Sci Transl Med. 2012;4:137ra76.
  2. Fan HC, Gu W, Wang J, Blumenfeld YJ, El-Sayed YY, Quake SR. Non-invasive prenatal measurement of the fetal genome. Nature. 2012;487:320-324. Abstract
  3. Committee on Bioethics. Ethical issues with genetic testing in pediatrics. Pediatrics. 2001;107:1451-1455. Abstract
  4. National Society of Genetic Counselors. Position Statement: Prenatal and Childhood Testing for Adult-onset Disorders. 1995. http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx#PrenatalChildTestingAdultOnsetAccessed July 12, 2012.
  5. American College of Obstetrics and Gynecology. ACOG Committee Opinion: Sex Selection; February 2007 (reaffirmed 2011). http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Ethics/Sex_SelectionAccessed July 12, 2012.

Medscape Genomic Medicine © 2012 WebMD, LLC

Retrieved from: http://www.medscape.com/viewarticle/771190?src=nl_topic


Early detection of ASDs

In Autism Spectrum Disorders, Neuropsychology, School Psychology on Wednesday, 26 September 2012 at 06:54

ASD’s Can Be Diagnosed in Patients as Young as 12 Months

Fran Lowry & Hien T. Nghiem, MD

Clinical Context

Autism-spectrum disorders (ASDs) are neurodevelopmental disorders diagnosed by clinical observation of core behavioral symptoms. The prevalence of ASDs is estimated to be approximately 1% of the general population and is typically diagnosed in the preschool years. However, it has been reported that behavioral risk signs of ASDs may be evident before 12 months of age.

By 9 to 12 months of age, infants who will eventually receive a diagnosis of ASD may demonstrate the absence of social communicative features, such as shared affective engagement, imitation, social orienting, and joint attention, and present with unusual sensory features such as repetitive play, sensory preoccupations, emotional dysregulation, hyporesponsiveness to novel stimuli, and atypical motor behaviors. The First Year Inventory (FYI) is a parent-report measure designed to identify 12-month-old infants at risk for ASD. FYI taps behaviors that indicate risk in the developmental domains of sensory–regulatory and social–communication functioning.

The aim of this study is to determine an effective FYI scoring cutoff for most accurately indentifying infants who are at risk for a later diagnosis of ASD. The aim was met by conducting a follow-up of 699 children at 3 years of age from a community sample whose parents completed the FYI when their children were 12 months old.

Study Synopsis and Perspective

A questionnaire for parents is a promising tool for identifying 12-month-old infants who are at risk for an eventual diagnosis of ASD, new research shows.

A longitudinal follow-up study showed that 31% of children identified by the inventory as being at risk for ASD at 12 months had a confirmed diagnosis by age 3 years.

In addition, 85% of the children identified at 12 months had a developmental disability or concern by age 3 years, coauthor Grace Baranek, PhD, from the University of North Carolina School of Medicine, Chapel Hill, told Medscape Medical News.

“These children have the advantage of being enrolled in an intervention sooner and being tracked sooner than they would normally be, because most of the screenings that are recommended by the American Academy of Pediatrics happen at 18 or 24 months of age,” Dr. Baranek said.

Led by Lauren M. Turner-Brown, PhD, who is also from the University of North Carolina School of Medicine, the study was published online July 10 in Autism: The International Journal of Research & Practice.

Critical Changes

The FYI was developed specifically for 12-month-old infants because this age seems to map onto a period of critical developmental and neurobiological changes that are occurring in many infants who will eventually be diagnosed with ASD, she explained.

The current study was carried out to determine the effectiveness of the inventory in identifying infants at risk for a later diagnosis of ASD. In it, the parents of the 699 children who had completed the FYI when their child was 12 months old completed the additional screening questionnaires when their child reached the age of 3 years.

The parents and children were recruited through a community mailing that was based on North Carolina birth records.

In addition to the FYI, parents received the Social Responsiveness Scale–Preschool Version and the Developmental Concerns Questionnaire, which asked specific questions about parent concerns and child diagnoses. They also received $5.00 to encourage participation in the study.

The inventory identified 6 children with ASD and 3 children with pervasive developmental disorder–not otherwise specified.

Sooner Is Better

A high score in the sensory regulatory domain, which looked at such things as unusual behaviors with play, repetitive behaviors, unusual responses to sensory things such as light and sounds, and day-to-day regulatory patterns such as feeding, sleeping, and eating, was an important predictor of a future diagnosis of ASD, Dr. Baranek said.

Scoring badly in the social communication domain, especially when accompanied by a high score in the sensory regulatory domain, was also predictive, she said. “What we are finding is that although we can identify a lot of children who go on to have autism through their lack of social communicative abilities, the sensory regulatory items help us to more specifically identify the kids with autism so we’re not overidentifying just children with language delay.”

Once the FYI tool is refined, Dr. Baranek said, she and her team would like to see it used in primary care settings at the 12-month baby check, where physicians, nurse practitioners, and early interventionists could screen the child and use the inventory as a basis for progressive surveillance.

“The sooner we can identify any child who has a concern, the sooner they can be referred for more comprehensive evaluation and be connected with support services,” she said.

Significant Impact

Autism Society board chairman Jim Ball agreed. Commenting on this work for Medscape Medical News, Ball said: “Early screening and diagnosis can have a significant impact in an individual’s life, leading to improved educational and social outcomes, as well as employment and independent living in adulthood.”

He added that it is a priority of the Autism Society “to ensure all families know the signs of autism, have access to expert diagnosticians, receive appropriate services, and transition effectively into adulthood.”

The study was funded in part by the National Institutes of Health, Autism Speaks, and the Ireland Family Foundation. Dr. Turner-Brown, Dr. Barane, and Ball have disclosed no relevant financial relationships.

Autism. Published online July 10, 2012.

Study highlights

  • Families who participated in the FYI normative study and who gave consent to be recontacted were invited to participate in this longitudinal follow-up.
  • There were 2 phases: the initial FYI screening mailing at 12 months of age and the subsequent follow-up mailing at age 3 years.
  • At 3 years, parents of 699 children completed the Social Responsiveness Scale–Preschool version and the Developmental Concerns Questionnaire to determine developmental outcomes.
  • In addition, children deemed at risk for ASD on the basis of liberal cut points on the FYI, Social Responsiveness Scale–Preschool, and/or Developmental Concerns Questionnaire were invited for in-person diagnostic evaluations.
  • 38 families participated in the in-person diagnostic assessments. In addition to the FYI, Social Responsiveness Scale–Preschool, and Developmental Concerns Questionnaire, the 38 children who received further in-person diagnostic evaluation also completed the Mullen Scales of Early Learning, the Vineland Adaptive Behavior Scale, and the Autism Diagnostic Observation Schedule.
  • A “best estimate” diagnostic outcome was determined and divided into 1 of 4 categories: diagnosis of ASD; diagnosis of other developmental disability; no professional diagnosis, but developmental concerns noted or observed; and no developmental concerns.
  • 9 children had a confirmed diagnosis of ASD from the sample of 699 children, representing 1.3% of this sample.
  • A total of 43 children (6%) were in the diagnosed or treated group for non-ASD developmental problems.
  • An additional 82 (12%) children were in the developmental concerns group.
  • Finally, 574 (82%) of 699 children were in the no concerns group.
  • According to the receiver operating characteristic (ROC) analyses, “a total risk score…of 19.2, which is at or above the 96th percentile, was chosen as the best cutoff score.”
  • A second ROC analysis was performed to calculate the optimal cutoffs for each of the 2 FYI domains.
  • For the social communication domain, “a domain score of 22.5, which is at the 94th percentile, yielded the optimal classification of children with ASD at age 3.”
  • “For the sensory-regulatory domain, a score of 14.75, which is at the 88th percentile, yielded optimal classification of children with an ASD diagnosis at age 3.”
  • The ROC analyses determined that a 2-domain cutoff score yielded optimal classification of children: 31% of those meeting algorithm cutoffs had ASD and 85% had a developmental disability or concern by age 3 years.
  • Limitations of the study included the following:
    • lack of design as an epidemiological study,
    • lack of generalizability because the families who participated in the study tended to be more educated and less racially diverse,
    • that unidentified children were probably missed by current measures, and
    • the feasibility of such large-scale diagnostic protocols.

Clinical Implications

  • By 9 to 12 months of age, infants who will eventually receive a diagnosis of ASD may demonstrate the absence of social communicative features and the presence of unusual sensory features.
  • These results suggest that the FYI is a promising tool for identifying 12-month-old infants who are at risk for an eventual diagnosis of ASD.

Retrieved from: http://www.medscape.org/viewarticle/769367


First Direct Genetic Evidence for ADHD Discovered-2010

In ADHD, ADHD Adult, ADHD child/adolescent, Genes, Genomic Medicine, Neuropsychology, Psychiatry, School Psychology on Tuesday, 25 September 2012 at 06:20

an older article, but one i thought worthy of posting.

First Direct Genetic Evidence for ADHD Discovered

Caroline Cassels

September 29, 2010 — New research provides the first direct evidence that attention-deficit/hyperactivity disorder (ADHD) is genetic.

In a study published online September 30 in The Lancet, investigators from the University of Cardiff in the United Kingdom say their findings, which show that ADHD has a genetic basis, suggest it should be classified as a neurodevelopmental and not a behavioral disorder.

“We’ve known for many years that ADHD may well be genetic because it tends to run in families in many instances. What is really exciting now is that we’ve found the first direct genetic link to ADHD,” principal investigator Anita Thapar, MD, told reporters attending a press conference to unveil the study results.

In the genomewide analysis, 366 children 5 to 17 years of age who met diagnostic criteria for ADHD but not schizophrenia or autism and 1047 matched controls without the condition were included. Researchers found that compared with the control group without ADHD, children with the disorder were twice as likely — approximately 15% vs 7% — to have copy number variants (CNVs).

CNVs, explained study investigator Nigel M. Williams, PhD, are sections of the genome in which there are variations from the usual 2 copies of each chromosome, such that some individuals will carry just 1 (a deletion) and others will have 3 or more (duplications).

“If a gene is included in one of these copy number variants, it can have deleterious consequences,” said Dr. Williams.

Shared Biological Link

The study authors note that the increased rate of CNVs was particularly high among children with a combination of ADHD and learning disabilities but “there was also a significant excess in cases with no such disability.”

The researchers also found that CNVs overlap with chromosomal regions that have previously been linked to autism and schizophrenia. Although these disorders are thought to be completely separate, there is some overlap between ADHD and autism in terms of symptoms and learning difficulties.

We’ve looked at only 1 class of variation, but it’s an important one because it has been linked to other brain disorders.

This finding suggests there may be a shared biological basis for the 2 conditions and, according to investigators, provides the first direct evidence that ADHD is a neurodevelopmental condition.

“We found that the most significant excess of these types of copy number variants was on a specific region of chromosome 16. This chromosomal region includes a number of genes, including one that affects brain development,” said Dr. Thapar.

The team’s research marks the start of the “unraveling of the genetics” of ADHD, according to Dr. Thapar.

“We’ve looked at only 1 class of variation, but it’s an important one because it has been linked to other brain disorders,” she said.

Implications for DSM-5?

Dr. Thapar added that the study results also have direct implications for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is currently under development by the American Psychiatric Association.

A “huge debate” about whether ADHD should be classified as a behavioral or neurodevelopmental disorder is ongoing. However, she said, these findings should help put this controversy to rest.

“Our results clearly show that ADHD should be considered a neurodevelopmental disorder,” she said.

In fact, Dr. Thapar noted that the study findings have been submitted to one of the DSM-5 work groups for consideration in the development of the new manual.

The investigators note that despite epidemiologic evidence derived from twin studies showing high heritability and the fact that ADHD is often accompanied by learning disabilities, there is still a great deal of public misunderstanding about the disorder.

Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma.

“Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma,” said Dr. Thapar.

Although there are no immediate treatment implications, Dr. Thapar said she hopes the research will have an immediate impact in terms of shifting public perception about ADHD and fuel further research into the biological basis of the disorder with a view to developing better, more effective therapies for affected individuals.

In an accompanying editorial, Peter H. Burbach, PhD, from the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands, writes, “The first gains beyond today’s study might be initial insights into the pathogenesis and neurobiology of brain development as influenced by these genetic variants. This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient’s genotype.”

Lancet. Published online September 30, 2010.

Retrieved from: http://www.medscape.com/viewarticle/729652

coming soon to a bookstore near you!

In ADHD, ADHD Adult, ADHD child/adolescent, Neuropsychology, School Psychology, Uncategorized on Monday, 24 September 2012 at 16:47

Psychometric Analysis of the New ADHD DSM-V Derived Symptoms

Ahmad Ghanizadeh

BMC Psychiatry. 2012;12(21) © 2012 BioMed Central, Ltd.

Abstract and Introduction

AbstractBackground Following the agreements on the reformulating and revising of ADHD diagnostic criteria, recently, the proposed revision for ADHD added 4 new symptoms to the hyperactivity and Impulsivity aspect in DSM-V. This study investigates the psychometric properties of the proposed ADHD diagnostic criteria.
Method ADHD diagnosis was made according to DSM-IV. The parents completed the screening test of ADHD checklist of Child Symptom Inventory-4 and the 4 items describing the new proposed symptoms in DSM-V.
Results The confirmatory factor analysis of the ADHD DSM-V derived items supports the loading of two factors including inattentiveness and hyperactivity/impulsivity. There is a sufficient reliability for the items. However, confirmatory factor analysis showed that the three-factor model is better fitted than the two-factor one. Moreover, the results of the exploratory analysis raised some concerns about the factor loading of the four new items.
Conclusions The current results support the two-factor model of the DSM-V ADHD diagnostic criteria including inattentiveness and hyperactivity/impulsivity. However, the four new items can be considered as a third factor.


Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children and adolescents. Its rate in community samples is variably reported. A study reported the rate of 5.29%.[1] Meanwhile, the rate of its screening symptoms is much higher, reaching up to 10.1% in school age children.[2] This high rate of ADHD prevalence emphasizes the need for accurate identification and diagnosis of ADHD.[3]

There has been a recent significant argument or controversy regarding the necessity of reformulating and revising ADHD criteria.[1,4,5] For example, recent criticism of the current ADHD subtypes and the suggestion of including age-specific ADHD criteria in DSM V should be considered.[6] In addition, the current ADHD subtypes are frequently criticized.[3] Some researchers are interested in introducing ADHD-inattentive type as a learning disorder.[7] Furthermore, there is a debate whether oppositional defiant disorder should be considered as a type of ADHD.[8,9] Girls with ADHD are underdiagnosed in the community.[6] Moreover, the impact of the change in the age of the onset has been investigated.[10]

Given that the proposed DSM-V criteria for ADHD are available and would be implemented in the near future,[11] it is advised that their psychometric properties and modifications be studied before their clinical application. To the best of the author’s knowledge, there are no published studies investigating the psychometric properties of the proposed ADHD diagnostic criteria for DSM-V.

DSM-IV defines ADHD as a cluster of symptoms; the patient must have at least six or more out of the 9 symptoms of inattention and/or six or more out of the 9 symptoms of hyperactivity/impulsivity.[12] The proposed revision of ADHD by American Psychiatric Association added 4 new symptoms to the Hyperactivity and Impulsivity aspect in DSM- V. These four symptoms are: “Tends to act without thinking, such as starting tasks without adequate preparation or avoiding reading or listening to instructions, may speak out without considering consequences or make important decisions on the spur of the moment, such as impulsively buying items, suddenly quitting a job, or breaking up with a friend”, “Is often impatient, as shown by feeling restless when waiting for others and wanting to move faster than others, wanting people to get to the point, speeding while driving, and cutting into traffic to go faster than others”, “Is uncomfortable doing things slowly and systematically and often rushes through activities or tasks”, and “Finds it difficult to resist temptations or opportunities, even if it means taking risks (A child may grab toys off a store shelf or play with dangerous objects; adults may commit to a relationship after only a brief acquaintance or take a job or enter into a business arrangement without doing due diligence)”.[11]

The aim of this study was to investigate the psychometric properties of the proposed ADHD symptoms in DSM-V. In the first step, factor analyses were conducted to assess the loadings for the symptoms. Then, the convergent and discriminative validity of the categories of inattentiveness and hyperactivity-impulsivity of DSM-V ADHD symptoms were assessed. Finally, the internal reliability of the inattentiveness and hyperactivity- impulsivity was calculated.


106 children, who were consecutive referrals to a university affiliated Child and Adolescent Psychiatry Clinic in Shiraz, Iran, participated in this study. All of the children and adolescents were interviewed face to face by a board certified Child and Adolescent psychiatrist. In addition, at least one of their parents or caregivers was interviewed face to face as a collateral information resource.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, DSM-IV diagnostic criteria was used to make psychiatric diagnoses.[12] Interviews were conducted according to the Farsi version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children.[13]

Parents reported ADHD symptoms by completing the ADHD checklist of child symptom inventory-4.[14–16] The ADHD checklist of child symptom inventory-4 includes 18 symptoms. The symptoms are categorized into two groups of inattentiveness and hyperactive/impulsivity symptoms. The inattentiveness symptoms category consists of 9 symptoms according to DSM-IV. The category of hyperactive/impulsivity symptoms consists of 9 symptoms according to DSM-IV as well. In fact, the symptoms are the DSM-IV diagnostic criteria. There is a 5-point Likert response scale for the symptoms. The responses ranged from “never,” “sometimes,” “often,” to “almost always”. Scores 0 and 1 were assigned to the categories of “never” and “sometimes”, respectively. The categories of “often” and “almost always” were assigned to 2 and 3, respectively. The range of scoring for each of inattentiveness and hyperactivity-impulsivity categories was from 0 to 9. The Farsi version of this checklist has enough reliability, convergent and discrimination validity[15] and has been used in many studies.[17–19] The internal reliability of this checklist for ADHD-inattentive type, ADHD-Hyperactive impulsive type, and combined type of ADHD is 0.81, 0.85, and 0.83, respectively.[14]

The four new items proposed by DSM-V to be added to ADHD diagnostic criteria were translated into Farsi and back translated into English by a bilingual child and adolescent psychiatrist and a psychologist. Every effort was made to preserve the concept of each symptom. After a pilot study on children referred to the clinic, the final version was used in the current study. The responses to these symptoms were in the Likert scale ranging from “never,” “sometimes,” “often,” to “almost always”.

The children and parents or caregivers gave their assent or informed written consent for voluntary participation in this study. This study was approved by the Ethics Committee of Shiraz University of Medical Sciences.


SPSS statistical software was used to analyze the data. A factor analysis with varimax rotation was conducted to examine the factor structure of the ADHD DSM-V symptoms. The Kaiser-Meyer-Olkin Measure and the Bartlett’s test of sphericity were conducted. Internal consistency was examined using Cronbach’s tests.

One-, two-, three-factor models of confirmatory factor analysis were also conducted using LISREL 8.54 software. The convergent and discriminative validity of ADHD symptoms were analyzed using Pearson’s r correlation coefficient.

Another factor analysis was also conducted including the four newly proposed symptoms to examine item loading of the 13 symptoms of DSM-V derived hyperactivity- impulsivity symptoms. Here, the symptoms of inattentiveness were not included in the analysis. This analysis was conducted to examine whether the 13 items could be divided into two categories of hyperactivity and impulsivity.

Another factor analysis was conducted including the DSM-IV derived inattentiveness symptoms and the four new symptoms proposed in DSM-V. The symptoms of hyperactivity-impulsivity of DSM-IV were not included.


The sample included 84 (79.2%) boys and 22 (20.8%) girls. The age range of the children and adolescents was 5.5 to 17years. Their mean age was 9.1(SD = 2.5) years.

The Kaiser-Meyer-Olkin Measure was 0.76. It shows the adequacy of sampling. The Bartlett’s test of sphericity was less than 0.001. These results indicate that the data are suitable for factor analysis. The factor loading of the principal component analysis is indicated in Table 1. The factor of Hyperactivity-Impulsivity explained 30.4% (eigenvalue = 6.7) of the total variance. The factor of Inattentiveness accounted for 12.1% (eigenvalue = 2.6). Nearly all of the symptoms of inattentiveness were loaded in one factor. All of the Hyperactivity-Impulsivity symptoms were loaded on another factor. Three out of the four newly proposed ADHD separate symptoms were loaded on the factor including inattentiveness symptoms.


Table 1. Principal component analysis of the ADHD DSM-V checklist by rotated method of varimax

Component DSM-V symptoms Hyperactivity- Impulsivity
ADHD- item 1- makes careless mistakes −.049 .600
ADHD- item 2- sustaining attention .032 .731
ADHD- item 3- listening when spoken to .323 .319
ADHD- item 4- follows instructions .354 .515
ADHD- Item 5- organizing tasks .164 .775
ADHD-Item 6 – sustained mental effort −.097 .784
ADHD- item 7- loses things .185 .527
ADHD- item 8- distracted by extraneous stimuli .223 .536
ADHD- item 9- forgetful in daily activities .157 .486
ADHD- item10- fidgets with hands .532 .227
ADHD- item11- leaves seat in classroom .657 .206
ADHD- item 12- runs about .638 .178
ADHD- item 13- playing or leisure activities .864 −.013
ADHD- item 14- often “on the go” .800 −.008
ADHD- item 15- talks excessively .726 .152
ADHD- item 16- blurts out answers .663 .134
ADHD- item 17- awaiting turn .625 .335
ADHD- item 18- interrupts or intrudes on others .713 .086
ADHD- item 19- act without thinking .272 .412
ADHD- item 20- impatient .431 .330
ADHD- item 21- uncomfortable doing things slowly and systematically .358 .430
ADHD- item 22- difficult to resist temptations or opportunities .236 .399

Extraction Method: Principal Component Analysis. Rotation Method: Varimax with Kaiser Normalization.

In order to test which of the various models gives the best fit to the data, three confirmatory factor analyses were conducted. A one-factor model was not a good fit (Chi- square = 384.65, df = 209, P value 0.0001, Root Mean Square Error of Approximation (RMSEA) = 0.098, Non-normed Fit index (NNFI) = 0.96, Comparative Fit index = 0.96.).

A two-factor model fit well. The results of two-factor model confirmatory factor analysis showing the correlation between inattentiveness and hyperactivity/impulsivity factors that was .56 are displayed in Table 2.

Table 2. The two-factor model of Confirmatory Factor Analysis of the ADHD DSM- V Checklist

Component DSM-V symptoms Hyperactivity- Impulsivity
ADHD- item 1- makes careless mistakes .49
ADHD- item 2- sustaining attention .71
ADHD- item 3- listening when spoken to .53
ADHD- item 4- follows instructions .73
ADHD- Item 5- organizing tasks .81
ADHD-Item 6 – sustained mental effort .66
ADHD- item 7- loses things .57
ADHD- item 8- distracted by extraneous stimuli .63
ADHD- item 9- forgetful in daily activities .56
ADHD- item10- fidgets with hands .64
ADHD- item11- leaves seat in classroom .72
ADHD- item 12- runs about .71
ADHD- item 13- playing or leisure activities .84
ADHD- item 14- often “on the go” .81
ADHD- item 15- talks excessively .76
ADHD- item 16- blurts out answers .69
ADHD- item 17- awaiting turn .76
ADHD- item 18- interrupts or intrudes on others .72
ADHD- item 19- act without thinking .49
ADHD- item 20- impatient .62
ADHD- item 21- uncomfortable doing things slowly and systematically .58
ADHD- item 22- difficult to resist temptations or opportunities .51

Chi-square = 384.65, df = 209, P valu < 0.0001, Root Mean Square Error of Approximation (RMSEA) = 0.098, Non-normed Fit index (NNFI) = 0.96, Comparative Fit index = 0.96.

However, a three-factor model of confirmatory factor analysis also fit well and it was better than the two-factor model (Table 3).

Table 3. The three-factor model of Confirmatory Factor Analysis of the ADHD DSM-V Checklist

Component Newly DSM-V symptoms Hyperactivity- Impulsivity
Inattentiveness added items
ADHD- item 1- makes careless mistakes .49
ADHD- item 2- sustaining attention .71
ADHD- item 3- listening when spoken to .52
ADHD- item 4- follows instructions .72
ADHD- Item 5- organizing tasks .82
ADHD-Item 6 – sustained mental effort .67
ADHD- item 7- loses things .57
ADHD- item 8- distracted by extraneous stimuli .63
ADHD- item 9- forgetful in daily activities .56
ADHD- item10- fidgets with hands .65
ADHD- item11- leaves seat in classroom .74
ADHD- item 12- runs about .73
ADHD- item 13- playing or leisure activities .86
ADHD- item 14- often “on the go” .83
ADHD- item 15- talks excessively .78
ADHD- item 16- blurts out answers .71
ADHD- item 17- awaiting turn .78
ADHD- item 18- interrupts or intrudes on others .74
ADHD- item 19- act without thinking .63
ADHD- item 20- impatient .80
ADHD- item 21- uncomfortable doing things slowly and systematically .78
ADHD- item 22- difficult to resist temptations or opportunities .66

Chi-square = 31.84, df = 206, P valu < 0.0001, Root Mean Square Error of Approximation (RMSEA) = 0.077, Non-normed Fit index (NNFI) = 0.99, Comparative Fit index = 0.99.

The factor loading of the second component analysis including only the symptoms of hyperactivity-impulsivity of DSM-V is displayed in Table 4. The Kaiser-Meyer-Olkin Measure was 0.83. Bartlett’s test of sphericity was less than 0.001. It shows that all of the symptoms of the ADHD DSM-IV derived are loaded in one factor. Meanwhile, the four new symptoms proposed in DSM-V are loaded in another factor.

Table 4. Principal components analysis of the hyperactivity-impulsivity symptoms of ADHD DSM-V Checklist

Hyperactivity-impulsivity symptoms
1 2
ADHD- item10- fidgets with hands .566 .123
ADHD- item11- leaves seat in classroom .666 .214
ADHD- item 12- runs about .629 .225
ADHD- item 13- playing or leisure activities .834 .111
ADHD- item 14- often “on the go” .771 .157
ADHD- item 15- talks excessively .753 .154
ADHD- item 16- blurts out answers .682 .112
ADHD- item 17- awaiting turn .574 .396
ADHD- item 18- interrupts or intrudes on others .717 .132
ADHD- item 19- act without thinking .207 .496
ADHD- item 20- impatient .208 .794
ADHD- item 21- uncomfortable doing things slowly and systematically .187 .755
ADHD- item 22- difficult to resist temptations or opportunities .022 .781

Extraction Method: Principal Component Analysis. Rotation Method: Varimax with Kaiser Normalization.

The principal component analysis including the DSM-IV derived inattentiveness symptoms and the four new symptoms proposed in DSM-V indicated the two factor loading (Table 5). This analysis indicates that all of the inattentiveness symptoms are loaded in one factor and the new symptoms proposed in DSM-V are loaded in another factor.

Table 5. Principal component analysis including the DSM-IV derived inattentiveness symptoms and the four new symptoms proposed in DSM-V

Inattentiveness symptom of DSM-IV and new proposed symptoms in DSM-V
1 2
ADHD- item 1- makes careless mistakes .676 −.045
ADHD- item 2- sustaining attention .780 .079
ADHD- item 3- listening when spoken to .486 .122
ADHD- item 4- follows instructions .551 .322
ADHD- Item 5- organizing tasks .686 .386
ADHD-Item 6 – sustained mental effort .667 .192
ADHD- item 7- loses things .414 .341
ADHD- item 8- distracted by extraneous stimuli .450 .367
ADHD- item 9- forgetful in daily activities .579 .057
ADHD- item 19- act without thinking .275 .565
ADHD- item 20- impatient .069 .785
ADHD- item 21- uncomfortable doing things slowly and systematically .136 .793
ADHD- item 22- difficult to resist temptations or opportunities .058 .750

Extraction Method: Principal Component Analysis. Rotation Method: Varimax with Kaiser Normalization.

The convergent and discriminative validity for the whole 22 symptoms proposed for ADHD in DSM-V were calculated. The range of convergent validity for the symptoms of inattentiveness was from 0.504 to 0.772 and that of discriminative validity for the symptoms of inattentiveness was from 0.017 to 0.427. Also, the range of convergent validity for the symptoms of hyperactivity-impulsivity was from 0.42 to 0.770 and that of discriminative validity for the symptoms of hyperactivity-impulsivity was from 0.12 to 0.39.

The alpha coefficient for the whole 24 symptoms of ADHD in DSM-V was 0.88. The alpha for the DSM-V hyperactivity-impulsivity was 0.87. It was 0.80 for DSM-IV inattention.


To the best of the author’s knowledge, this is the first study investigating psychometric and factor structure of ADHD DSM-V derived symptoms. So, it is not possible to compare the current results with those of other studies. Confirmatory factor analysis confirmed the proposed two-factor loading of inattentiveness and hyperactivity/impulsivity for the new ADHD DSM-V criteria. However, the three-factor model of confirmatory factor analysis showed that the four new items can be considered as the third factor.

The results indicate that convergent and discriminative validity for ADHD DSM-V derived inattention symptoms are sufficient. Although the symptoms of hyperactivity- impulsivity are discriminated from inattentiveness symptoms, the convergent validity of the four newly proposed symptoms in DSM-V is not as high as that of the 9 symptoms derived from DSM-IV. The three new criteria for hyperactivity/impulsivity were loaded in inattentiveness factor rather than in hyperactivity-impulsivity factor. These may not support the fact that the 4 proposed symptoms for revision of ADHD exactly describe hyperactivity-impulsivity symptoms. However, the internal consistency and reliability of the inattentiveness and hyperactive/impulsivity symptoms are high.\

Considering the factor loading of the four newly proposed symptoms added to DSM-V, there is a concern that inattentiveness symptoms may falsely increase the diagnosis of ADHD-hyperactive/impulsive type or combined type of ADHD. It means that the symptoms which are loaded as inattentive symptoms may lead to subthreshold ADHD- hyperactive/impulsive type using DSM-IV, while fulfilling criteria of ADHD- hyperactive/impulsive type using DSM-V.

With respect to the fact that the better diagnoses and classification of children with ADHD could lead to a better treatment, more discussion and justification about the new items are required. Probably, future studies should investigate the neuropsychological functioning of children with ADHD for the classification of the subtypes of ADHD. The current results indicated that continued research is required to reach accurate diagnostic criteria for making accurate ADHD diagnoses.

There is some overlap between ADHD symptoms and ODD in DSM-IV.[20] ODD symptoms are properly differentiated from ADHD. However, two items of the ADHD including “Often has trouble organizing activities” and “Often runs about or climbs when and where it is not appropriate” are loaded in the oppositional defiant disorder component rather than ADHD component.[20] Another concern is whether the new added symptoms in DSM-V are well differentiated from ODD symptoms. This needs further studies.

There are some limitations in this study which need to be considered. This study was conducted on a clinical sample of children and adolescents with ADHD. Further studies with larger sample size including community sample with a wider age rage are recommended. The children and their parents were the sources of information. Including other informants such as teachers is also recommended. This study is based on one sample in a specific geographical area. In addition, the use of translation instead of the actual questionnaire is another limitation. A multi-site approach with a more limited age range would be required to appropriately assess the psychometric properties of the proposed items of a classification used worldwide.

Despite the above-mentioned limitations, this is the first study that assesses psychometric properties of ADHD DSM-V derived symptoms. In addition, the children, adolescents and parents were interviewed face to face using a well known semi- structured interview. Moreover, all the interviews were conducted by a Board-certified child and adolescent psychiatrist.


The findings of present study support the two-factor model of the DSM-V ADHD diagnostic criteria including inattentiveness and hyperactivity/impulsivity. Nevertheless, the four new items can be considered as a third factor.


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Retrieved from: http://www.medscape.com/viewarticle/764516

Drug Therapy for Autism

In Autism Spectrum Disorders, Medication, Neuropsychology, Psychiatry, Psychopharmacology on Monday, 24 September 2012 at 16:10

Autism Patients Might Benefit from Drug Therapy

By SYDNEY LUPKIN | ABC News – Wed, Sep 19, 2012 2:37 PM EDT

Researchers have found a drug that can help patients with Fragile X syndrome, the most common cause of inherited intellectual impairment (formerly known as mental retardation), stay calm in social situations by treating their anxiety.

Dr. Elizabeth Berry-Kravis and her team found that a drug called Arbaclofen reduced social avoidance and repetitive behavior in Fragile X patients, especially those with autism, by treating their anxiety. The drug increases GABA, a chemical in the brain that regulates the excitatory system in Fragile X patients, who have been known to have too little GABA to do the job otherwise, causing their excitatory systems to “signal out of control” and make them anxious.

Such patients have been known to cover their ears or run away at their own birthdays because they are overwhelmed by the attention, but one trial participant said he was able to enjoy his birthday party for the first time in his life while he was on Arbaclofen, she said.

“I feel like it’s kind of the beginning of chemotherapy when people first realized you could use chemotherapy to treat cancer patients instead of just letting them die,” said Berry-Kravis, a professor of neurology and biochemistry at Rush University Medical Center in Chicago who has studied Fragile X for more than 20 years.

She said people used to think Fragile X patients couldn’t be helped either, but she and her team have proven that by using knowledge from existing brain mechanism studies, doctors can select medications to target specific problems in Fragile X patients’ brains.

Fragile X syndrome is a change in the FMRI gene, which makes a protein necessary for brain growth, and studies indicate it causes autism in up to one-third of patients diagnosed with it. Unlike Fragile X syndrome, which is genetic, autism is a behavioral diagnosis characterized by an inability to relate to other people or read social cues. Autism and Fragile X are linked, but not mutually exclusive. A core symptom of both is social withdrawal.

Sixty-three patients with Fragile X participated in Berry-Kravis’s placebo-controlled, double-blind clinical trial from December 2008 through March 2010. Of those, the patients with autism showed the biggest improvements in social behavior, Berry-Kravis said.

To psychologist Lori Warner, who directs the HOPE Center at Beaumont Children’s Hospital, the study is exciting because when her autistic patients are anxious, they often have a harder time learning the social cues they can’t read on their own.

“Reducing anxiety opens up your brain to be able to take in what’s happening in an environment and be able to learn from and understand social cues because you’re no longer frightened of the situation,” Warner said.

She works mostly with autism patients, and although some do have Fragile X as well, most do not.

Fragile X affects one in 4,000 men and one in 6,000 to 8,000 women, according to the Centers for Disease Control and Prevention.

Although Arbaclofen worked best on autistic Fragile X patients, further studies will be needed to prove whether it can help all autism patients, not just those with autism caused by Fragile X.

“There’s a difference between one person’s brain and another in how it’s set up,” Berry-Vargis said. “This is not a magic cure. It’s a step.”

Retrieved from: http://gma.yahoo.com/autism-patients-might-benefit-drug-therapy-183744169–abc-news-health.html

More on insomnia…

In Medication, Neuropsychology, Psychiatry on Thursday, 20 September 2012 at 06:30

Expert Interview – Emerging Concepts and Therapies in Insomnia: An Expert Interview With Daniel Buysse, MD

Daniel J. Buysse, MD, 2006


Editor’s Note:

Marni Kelman, MSc, Medscape Neurology & Neurosurgery Editorial Director, discussed emerging concepts and therapies in insomnia with Daniel Buysse, MD, Professor of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Insomnia in older adults, comorbid insomnia, new treatments on the horizon for insomnia, and new endpoints for therapeutic effectiveness of insomnia treatments were discussed.

Medscape: This issue of Current Perspectives in Insomnia includes a column on sleep disorders in older adults, with a focus on insomnia. What would you say is the impact of insomnia in older patients?

Dr. Buysse: The impact of insomnia in general is pretty wide-ranging, and some of those impairments are even greater in older people. Insomnia can have negative effects on a person’s mood the next day, on their concentration, on their energy level, or can cause fatigue or even sleepiness. Since older adults might experience these things for other reasons, insomnia tends to make them even worse.

Medscape: Are there any particular things that you take into consideration when you diagnose insomnia in an older patient?

Dr. Buysse: Because older adults will so commonly have medical or psychiatric comorbidity, it’s very important to look for those things. Older adults can have medical conditions that can cause pain, difficulty breathing, or impaired mobility, and all of those things can worsen insomnia. Older adults are also at risk for depression, which is the most common comorbid condition seen with insomnia. In addition, older adults are typically the ones who are taking the most medications, and because many medications can have effects on sleep, including insomnia, it’s very important to assess the effects of medications as well.

There are also a number of behavioral factors that can contribute to insomnia — things like going to bed early or spending too much time in bed — and those things, too, affect older adults disproportionately, since in older adults, limitations in daytime activities may leave them with fewer alternatives to going to bed. So, from both a medical perspective and a behavioral perspective, older adults are at risk.

There are a couple of sleep disorders that are more common in older adults that may be associated with insomnia symptoms, and those include restless legs syndrome and periodic limb movement disorder. There is almost certainly an increase in periodic limb movements with age, and again, this can lead to, or be associated with insomnia complaints. Older adults also have an increased incidence of sleep apnea, and compared to younger adults, sleep apnea may less commonly be associated with obesity, and less commonly associated with daytime sleepiness as the primary presenting complaint. The combination of sleep apnea with insomnia seems to be something that is disproportionately common in older adults.

The final sleep disorder that is common in older patients and that can cause insomnia is advanced sleep-phase syndrome. An individual with this syndrome feels very sleepy and goes to sleep early in the evening but then has insomnia characterized by early-morning awakening and an inability to return to sleep. This condition may be related to certain circadian changes that accompany aging.

Medscape: What special considerations do you take into account when you treat older patients with insomnia?

Dr. Buysse: With regard to medications, one needs to proceed a bit more cautiously for 2 reasons. First, older adults may have changes in drug-metabolizing enzymes, so they may metabolize drugs more slowly, or store drugs disproportionately longer because of an increase in the relative amount of body fat. This means that the same drug may have a longer than expected action in older adults. Second, older adults are typically on multiple medications, and some may have additive effects with some of the medications that we give for sleep.

With regard to behavioral treatments, I think the main thing to keep in mind is that older adults can and do benefit from those kinds of treatments as well. So the main message there is to not assume that older adults can’t learn these techniques; they can, and several studies have shown that they can be very effective.

Medscape: Are there particular types of medications that you use in the elderly and/or avoid?

Dr. Buysse: Generally, the approved hypnotic medications are appropriate for older adults, but you do need to be cautious, so it’s often wise to begin with a lower dose than you would use in younger and middle-aged adults. Because of the sensitivity that older people may have to the cognitive side effects of hypnotic drugs, in general, you would want to use a short-acting drug whenever possible to avoid the daytime cognitive and sedative consequences of hypnotic medications. The new hypnotic medication, ramelteon, may be particularly useful in older adults because it has very, very few — actually no — demonstrated cognitive side effects. So that may be a useful drug. The question there is whether it’s actually long enough acting to help with some of the sleep-maintenance problems that older adults might have.

Sedating antidepressants are pretty commonly used, as are antihistamines for the treatment of insomnia. Antihistaminic drugs should be approached with particular caution in the elderly because they often have anticholinergic effects that can worsen cognition and even lead to adverse consequences, such as delirium and urinary retention. One also needs to be careful when using sedating antidepressants in older adults.

Medscape: Another topic that we have discussed in this newsletter is insomnia associated with psychiatric and medical disorders. Are there particular considerations that you take into account when diagnosing those types of patients as well as treating them?

Dr. Buysse: The previous assumption was that if insomnia is associated with another condition, one would be best off just treating that other condition, and then the insomnia should get better. While there is clearly some evidence that treating comorbid conditions does lead to some improvement in insomnia, in many individuals insomnia may persist, even when the other disorder is adequately or optimally treated. In those cases, it may be useful to think of insomnia as a comorbid condition rather than as, strictly speaking, a symptom of that other disorder. If you think of insomnia as a comorbid condition, then in many cases it’s appropriate to direct treatment at the insomnia itself.

There is certainly emerging evidence that treating insomnia specifically does lead to improvement in sleep among patients with either medical conditions or psychiatric conditions. However, there is also a small, but growing, body of evidence that treating insomnia may actually lead to better outcomes of the comorbid medical or psychiatric condition itself.

Medscape: I would also like to ask for your feedback on emerging treatments for insomnia. Are there particular new therapeutic targets for therapy that you think are most promising?

Dr. Buysse: There are a lot of different therapeutic targets that are being examined, and I think the first general thing to say is that this is great because it’s unlikely that insomnia in all people results from the same problem. Therefore, having different ways to impact sleep just makes sense. The other point is that the regulation of sleep itself is very complex and involves multiple neurotransmitter systems. So again, having drugs that target different neurotransmitter systems just makes good sense.

Having said that, there are new agents under investigation that affect the GABA-benzodiazepine receptors and have modified-release preparations so that you can combine a reasonably long duration of action with a short half-life. That means that there is the possibility of providing adequate coverage of insomnia for the entire night, but rapid metabolism of the medication occurs toward the end of the night so that there are fewer daytime consequences.

That’s one strategy. Another strategy is to look at GABA reuptake or extrasynaptic GABA receptors. Other neurotransmitter systems are also being investigated, including serotonin 5HT2A receptors. Antagonists at that receptor have different effects on sleep, so that will be interesting to investigate. Different companies are looking into medications that interact with hypocretin or orexin receptors. That, too, promises, I think, to be a pretty exciting development.

Medscape: There has been some discussion about using new therapeutic endpoints for insomnia, for example, alertness, decreased depression, or decreased daytime napping. How do you feel about this, and what do you think are the most promising new endpoints that should be considered when looking at therapeutic effectiveness?

Dr. Buysse: I think that this is a very important area because patients with insomnia complain not only because their nighttime sleep is disturbed, but because that disturbance is associated with daytime consequences. Therefore, I think that the most interesting areas to look at are those that assess the daytime complaints presented by people with insomnia. One area is the routine assessment of mood symptoms and problems. We’ve been working on some data that show that it may be important not only to assess the person’s mood, but to evaluate how mood changes during the course of the day. So, looking at time-of-day effects may be very important. The second area to assess is fatigue, which is so commonly reported by people with insomnia and can be reliably measured with a number of rating scales. That should certainly be a focus of increased attention.

An area that has been somewhat perplexing, but very important, is the measurement of cognitive difficulties in people with insomnia. There have not been a lot of positive studies in this regard, so despite the fact that people complain of difficulty concentrating or problems with alertness, actually demonstrating impairments has generally not met with success. This may be due to the fact that the tools we have used have been of the wrong type or are not sensitive enough. So, I think trying to identify and develop tests that objectively measure daytime performance as related to the insomnia complaints would be very beneficial as well.

Medscape: What would you consider to be the biggest challenges in insomnia today?

Dr. Buysse: For behavioral and psychological treatments, the big challenge is making those treatments more widely available. We have several techniques that have demonstrated efficacy, but trying to really position them in the community so they have a wide impact is the challenge.

For medications, one of the biggest challenges is developing strategies for longer-term management of insomnia. We know that insomnia tends to be a chronic or recurring condition, and there is still uncertainty about the optimal way to manage chronic insomnia with medications.

The more general thing that I would say pertains to both behavioral and pharmacologic treatment: We really are in very substantial need of empirically supported treatment guidelines or treatment algorithms. We know that we have several efficacious treatments, but we don’t know how best to sequence them, how to target them to specific patients, and how to change from one to the other when the first treatment does not meet with success.


Hypnotic use and side effects

In Insomnia, Medication, Neuropsychology, Psychiatry on Tuesday, 18 September 2012 at 05:25

chronic insomnia and sleep deprivation are major issues affecting over 30% of  the u.s population.  approximately 10 million people are prescribed hypnotics to treat insomnia.  while the concurrent effects from untreated insomnia are vast, and hypnotic use may be the only viable option, it is suggested that one educate themselves on the effects related to untreated insomnia (see previous post titled “the state of sleep in the u.s.”) and options for treatment as well as recent research regarding the side-effects of some treatments.  

Hypnotic Use Linked With Increased Risk for Early Death

Megan Brooks & Laurie Barclay, MD


Clinical Context

In 2010, approximately 6% to 10% of US adults used a hypnotic drug for sleep problems. Earlier studies have suggested an association between hypnotic use and excess mortality rates.

The objectives of this study by Kripke and colleagues were to estimate the mortality risks and cancer risks associated with specific, currently popular hypnotics, using a matched cohort design and proportional hazards regression models. In addition, the investigators examined what degree of risk associated with hypnotic use could be explained by confounders and comorbid conditions.

Study Synopsis and Perspective

Adults who use hypnotics to help them sleep have a greater than 3-fold increased risk for early death, according to results of a large matched cohort survival analysis.

Hazard ratios were elevated in separate analyses for several commonly prescribed hypnotics and for newer shorter-acting drugs, the researchers say. The drugs included benzodiazepines, such as temazepam; nonbenzodiazepines, such as zolpidem, eszopiclone, and zaleplon; barbiturates; and sedative antihistamines.

“The take-home from the article is that the risks associated with hypnotics are very high, and certainly these possible risks outweigh any benefits of hypnotics,” first author Daniel F. Kripke, MD, co-director of research at the Scripps Clinic Viterbi Family Sleep Center in La Jolla, California, told Medscape Medical News.

“Our study is the 19th epidemiological study showing that hypnotics are significantly associated with excess mortality,” Dr. Kripke added, noting it is also the first to specify the drugs and the first to show dose-response. “Even considering that the epidemiologic studies show association and do not prove causality, the risks look much larger than the benefits,” Dr. Kripke added.

Their analysis also showed a 35% overall increased risk for cancer in hypnotics users. “The risks of hypnotics are similar to the risks of cigarettes,” Dr. Kripke said.

The associations were evident in every age but were greatest among those aged 18 to 55 years, the investigators note. “Rough order-of-magnitude estimates…suggest that in 2010, hypnotics may have been associated with 320,000 to 507,000 excess deaths in the USA alone,” they report.

The new report is published February 28 in BMJ Open.

Dr. Kripke, a long-time critic of hypnotics, emphasized that the data “apply only to the particular hypnotics studied when used as sleeping pills. They do not apply to drugs which were not tested.” Moreover, he said, they may not apply when the drugs are used other purposes, “in which they might be life-saving. Oddly enough, the data for use of benzodiazepines for anxiety may not be similar,” Dr. Kripke noted.

“Risks Outweigh Any Benefits”

In 2010, an estimated 6% to 10% of adults in the United States took a hypnotic drug to help them sleep, with the percentages probably higher in Europe, Dr. Kripke and colleagues note in their report.

Data for their analysis were derived from the electronic medical records of the Geisinger Health System, the largest rural integrated health system in the United States, serving a 41-county area of Pennsylvania with roughly 2.5 million people.

Study participants included 10,529 adults (mean age, 54 years) who received hypnotic prescriptions and 23,676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 years between 2002 and 2007.

“As predicted,” report the researchers, patients prescribed any hypnotic, even fewer than 18 pills per year, were significantly more likely to die during follow-up compared with those prescribed no hypnotics. A dose-response effect was evident, and the findings “were robust with adjustment for multiple potential confounders and consistent using multiple strategies to address confounding by health status,” they report.

Table 1. Risk for Death by Level of Hypnotic Use

Any Hypnotic

Hazard Ratio (95% Confidence Interval)

P Value

Up to 18 pills per year

3.60 (2.92 – 4.44)


18 – 132 pills per year

4.43 (3.67 – 5.36)


> 132 pills per year

5.32 (4.50 – 6.30)


Zolpidem was the most commonly prescribed hypnotic during the study interval, followed by temazepam; both were associated with significantly elevated risks for death, again in a dose-response fashion.

Table 2. Risk for Death with Zolpidem and Temazepam

Agent (mg/y)

Hazard Ratio (95% Confidence Interval)

P Value


5 – 130

3.93 (2.98 – 5.17)


130 – 800

4.54 (3.46 – 5.95)


> 800

5.69 (4.58 – 7.07)



10 – 240

3.71 (2.55 – 5.38)


240 – 1640

4.15 (2.88 – 5.99)


> 1640

6.56 (5.03 – 8.55)


“The death [hazard ratios] HR associated with prescriptions for less commonly prescribed hypnotic drugs were likewise elevated and the confidence limits of death hazards for each other hypnotic overlapped that for zolpidem, with the exception of eszopiclone, which was associated with higher mortality,” the investigators report.

Any hypnotic use in the upper third (>132 pills per year) was also associated with a modest but statistically significant increased risk for incident cancer (HR, 1.35; 95% CI, 1.18 – 1.55). The cancer risk was nearly 2-fold higher with temazepam (>1640 mg per year; HR, 1.99; 95% CI, 1.57 – 2.52).

Study Raises “Important Concerns”

Prior studies have shown multiple causal pathways by which hypnotics might raise the risk for death. For example, controlled trials have shown that hypnotics impair motor and cognitive skills, such as driving. Use of hypnotics has been linked to an increase in automobile crashes and an increase in falls due to hangover sedation. In some patients, hypnotics may increase or prolong sleep apneas and suppress respiratory drive. They may also increase incident depression.

“The meagre benefits of hypnotics, as critically reviewed by groups without financial interest… would not justify substantial risks,” the investigators write. They say a “consensus is developing that cognitive-behavioural therapy of chronic insomnia may be more successful than hypnotics.”

In a prepared statement, Trish Groves, MBBS, MRCPsych, editor-in-chief of BMJ Open, comments: “Although the authors have not been able to prove that sleeping pills cause premature death, their analyses have ruled out a wide range of other possible causative factors. So these findings raise important concerns and questions about the safety of sedatives and sleeping pills.”

American Academy of Sleep Medicine Urges Caution

In a statement, Nancy Collop, MD, president of the American Academy of Sleep Medicine (AASM) urged caution in interpreting these data.

“Although the study found that the use of hypnotic medication, or sleeping pills, was associated with an increased risk of mortality, a cause-and-effect relationship could not be established because the study only analyzed an insurance database,” Dr. Collop notes in the statement. “The authors also noted several other limitations to their study. For example, it was impossible for them to control for psychiatric conditions and anxiety, which is an area of significant concern to this study population.” In addition, she adds, those taking hypnotics had a “markedly greater rate of several comorbid health problems than the control group, suggesting they were a sicker population.”

AASM guidelines say that hypnotic medication prescribed appropriately and monitored carefully is a “reasonably” safe therapy that provides some improvement in people with insomnia, Dr. Collop notes in the statement. When possible, behavioral and cognitive therapies should be used and if needed supplemented with short-term use of hypnotics, the guidelines recommend. “Patients taking hypnotics should schedule regular follow-up visits with their physician, and efforts should be made to prescribe the lowest effective dose of medication and to reduce the medication’s usage when conditions allow,” the statement adds.

Effective treatment of insomnia is important because it’s associated with a “host” of comorbid conditions, including major depression and other psychiatric disorders, as well as increased for suicide, motor vehicle accidents, and possibly cardiovascular disease, Dr. Collop points out. Other research has shown widespread changes in physiology and the central nervous system associated with insomnia, and the “marked dysfunction and diminished quality of life” reported by some of those with insomnia are similar to that seen with major psychiatric or medical illnesses.

“We commend Drs. Kripke, Langer and Kline for contributing new scientific information to the study of sleep medicine,” Dr. Collop notes in the AASM statement. “We believe it is important for patients and physicians to be aware of how sleep issues impact health. But we caution physicians and patients to consider the years of research in support of limited hypnotics use, under the clinical guidelines of the AASM, before making any drastic changes in therapy.”

The AASM recommends that individuals with ongoing sleep problems should seek help from a board-certified sleep physician, “at one of 2,400 AASM-accredited sleep centers across the US.” A sleep center listing is found at the AASM’s site, www.sleepcenters.org.

In a competing interests statement, Dr. Kripke reports long-term criticism of hypnotic drugs at his nonprofit Web site. He also discloses a family interest in an investment corporation that has a small percentage of its assets in stock of sanofi-aventis and Johnson & Johnson. His 2 coauthors have disclosed no relevant financial relationships. Dr. Collop has disclosed no relevant financial relationships.

BMJ Open. Published online February 28, 2012. Abstract

Study Highlights

  • This matched cohort study took place at a large, integrated US health system.
  • The investigators extracted longitudinal electronic medical records for a 1-to-2 matched cohort survival analysis.
  • Patients who received hypnotic prescriptions (n = 10,529) were matched with 23,676 control participants with no hypnotic prescriptions.
  • Mean age was 54 years, and average duration of follow-up (between January 2002 and January 2007) was 2.5 years.
  • Data were adjusted for age, sex, smoking, body mass index, ethnicity, marital status, alcohol use, and history of cancer.
  • Cox proportional hazards models allowed calculation of HRs for death.
  • The Cox models were controlled for risk factors and used up to 116 strata, which exactly matched case patients and control participants by 12 classes of comorbidity.
  • Compared with patients who were prescribed no hypnotics, those who were prescribed any hypnotic had markedly increased hazards of dying.
  • There was a dose-response association. The HR was 3.60 (95% CI, 2.92 – 4.44) for 0.4 – 18 doses per year, 4.43 (95% CI, 3.67 – 5.36) for 18 to 132 doses per year, and 5.32 (95% CI, 4.50 – 6.30) for more than 132 doses per year.
  • In separate analyses, HRs were increased for several widely used hypnotics and for newer shorter-acting drugs, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates, and sedative antihistamines.
  • Among users in the highest tertiles of doses per year, the HRs for death were 5.3 for all hypnotics, 5.7 for zolpidem alone, and 6.6 for temazepam alone.
  • Patients in the highest tertile of hypnotic use had a significant (35%) increased risk for incident cancer (HR, 1.35; 95% CI, 1.18 – 1.55).
  • These findings were robust within groups having a comorbid condition, suggesting that the risks for death and cancer associated with hypnotic drugs were not explained by preexisting disease.
  • Hypnotic prescriptions were associated with increased diagnoses of esophageal regurgitation and peptic ulcer disease; the investigators note that increased regurgitation could cause esophageal damage and cancer.
  • On the basis of these findings, the investigators concluded that hypnotic prescriptions was associated with more than a 3-fold increased risk for death, even when the prescription was for less than 18 pills per year.
  • This association was also observed in separate analyses for several commonly used hypnotics and for newer, shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality rates.
  • Limitations of this study include possible residual confounding, lack of data on compliance with prescriptions, and inability to determine causality or to control for depression and other psychiatric symptoms.

Clinical Implications

  • Compared with control participants not receiving hypnotic prescriptions, patients receiving prescriptions for zolpidem, temazepam, and other commonly used hypnotics had a more than 3-fold risk for greater mortality in this matched cohort study. There appeared to be a dose-response relationship, but even patients prescribed less than 18 hypnotic doses per year had increased mortality rates.
  • Among patients prescribed hypnotics, the incidence of cancer was increased for several specific types of cancer, and those prescribed high doses had an increased overall rate of cancer of 35%.

ADHD into Adolescence

In ADHD, ADHD child/adolescent, ADHD stimulant treatment, Medication, Neuropsychology, School Psychology on Friday, 14 September 2012 at 05:26

Adolescent ADHD: Diagnosis and Initial Treatment

Scott H. Kollins, PhD


ADHD Into Adolescence

Longitudinal studies demonstrate that ADHD is a disorder that children do not simply outgrow as they reach adolescence.[1-5] Follow-up studies of children with ADHD estimate that the diagnosis persists in 50% to 80% of cases.[1,6-10] Studies of clinically referred adolescents with ADHD also indicate that the disorder continues into adolescence and is associated with various functional impairments, particularly when compared with nondiagnosed peers, including social competence, behavioral and emotional adjustment, school performance, and general quality of life.[11,12]

Although ADHD as a disorder is continuous from childhood into adolescence,[13] the persistence of ADHD into adolescence needs to be considered in the context of adolescence as a period of development in which there are many changes at multiple levels, including physical, psychological, and social changes. During this developmental period, adolescents typically experience a growing influence of peers and independence from family members.[14] For adolescents with a disorder like ADHD in which social and emotional impairment is common,[15] this transitional period may be particularly difficult. Cognitive demands increase along with greater independence from adult supervision (eg, multiple teachers with different teaching styles, amount and scope of homework) as children enter into middle and high school,[11] which requires greater self-regulation, a quality that is often impaired in those with ADHD.

Neuronal and hormonal developmental changes during adolescence can further influence how symptoms are expressed.[14] Related to these biologically based changes, adolescence also is a critical period neurobiologically, with more risk-taking behavior and drug and alcohol use, which correspond with notable changes in motivational and reward-related brain regions. Such behaviors can be problematic because adolescents are naturally more sensitive to the positive rewarding properties of various drugs and natural stimuli and less sensitive to the aversive properties of these stimuli.[16] These behavioral and neurobiological developmental changes in concert with social, hormonal, and physiological changes place adolescents at high risk for substance use.[17,18] ADHD is an additional risk factor for such substance use behavior (reviewed in greater detail below) and thus places adolescents with ADHD at greater risk during this critical developmental period.

Given such developmental changes, the presentation of ADHD changes in adolescence as well, including symptom presentation; although inattentive symptoms continue to be involved in the clinical characteristics of most patients, hyperactive symptoms decline in severity for many.[7,19-21] This symptom presentation continues to cause functional impairment in domains typically impaired in childhood, including academics.[22]

Adolescents with ADHD smoke at significantly higher rates than peers without ADHD and start smoking earlier, demonstrate a higher level of nicotine dependence, and have greater difficulty quitting than youth without ADHD. Some studies have estimated that 25% to 75% of adolescents with ADHD meet diagnostic criteria for ODD or CD. Although mood disorders are often seen in adolescents with ADHD, with an incidence of roughly 10% to 20%, they are less common than DBD. ADHD may be evidence of more severe bipolar disease. For example, ADHD is more common in those with childhood-onset bipolar disorder, which suggests that in some cases ADHD may signal an earlier onset, more chronic bipolar disorder.

ADHD and Comorbid Conditions in Adolescence

Comorbidity within populations of adolescents with ADHD is typically the norm rather than the exception. For example, in one clinical sample of patients 6 to 18 years old, more than half met the criteria for at least one comorbid disorder.[23] Disruptive behavior disorders, including ODD and CD, are particularly common.[24] In general population studies, ADHD increases the odds of ODD or CD by 10.7-fold.[25] Some studies have estimated that 25% to 75% of adolescents with ADHD meet the diagnostic criteria for ODD or CD.[14] In another study, ODD was comorbid among 54% to 67% of clinically referred 7- to 15-year-old children with ADHD.[23] In this study, differences in subtypes also emerged. ODD was significantly more common among those with combined and hyperactive-impulsive ADHD subtypes (50.7% and 41.9%, respectively) than with inattentive subtype (20.8%). Such rates are concerning not only because of the characteristics of these comorbid disruptive behavior disorders (eg, delinquency) that are dealt with in adolescence, but also because CD is a precursor to antisocial personality disorder in adulthood. Given that CD is commonly seen in children with ADHD and is a precursor to antisocial personality disorder, it is not surprising that rates of antisocial personality disorder (among additional forms of Axis II psychopathology) are elevated in adults with ADHD.[4,5,10,26,27]

SUDs are also common in adolescents with ADHD. In longitudinal studies of hyperactive children, the risk for SUDs ranges from 12% to 24% into adulthood.[8,10,26] Because adolescence is a time when initial exposure to substances occurs and because adolescence is also a developmental period during which susceptibility to the reinforcing effects of substances is heightened,[16-18] substance use in adolescence is a concern both as an outcome of current use and of continued risk for future use. This risk is further elevated among adolescents with ADHD. Individuals with ADHD engage in experimentation earlier than children without ADHD.[28,29] Although such findings indicate that the relationship between ADHD and SUDs is independent of comorbidity, CD is a strong predictor of risk for SUDs among children with ADHD when they reach adolescence and adulthood.[30-32] In addition, prospective studies indicate that children with ADHD and co-occurring CD or bipolar disorder are at a higher risk for SUDs during adolescence.[33-35]

Adolescents with ADHD smoke at significantly higher rates than peers without ADHD. Prevalence rates range from 10% to 46% for adolescents with ADHD vs 10% to 24% for adolescents without ADHD.[34,36,37] Even among nonclinical patient samples, there is a linear relationship between number of ADHD symptoms, lifetime risk of smoking, and age of onset of regular smoking.[38] Additional studies have demonstrated that youth with ADHD initiate smoking earlier, exhibit a higher level of nicotine dependence, have greater difficulty quitting than youth without ADHD, and are at an increased risk for becoming a regular cigarette smoker.[37,39] In addition, the relationship between ADHD and tobacco use has remained significant as an independent risk factor after accounting for comorbidity, including CD.[40,41]

Mood disorders are also common among adolescents with ADHD.[42] For example, in one study, 21.6% of children 6 to 18 years old who had ADHD also had a depressive disorder.[23] The combination of a major depressive disorder and a comorbid disruptive behavior disorder is a risk factor for suicidal behavior,[43] and both major depressive disorder and disruptive behavior disorder are common comorbidities in those with ADHD. One longitudinal study assessing childhood ADHD reported that the diagnosis of ADHD in children predicted adolescent depression and/or suicide attempts. In addition, female sex, maternal depression, and concurrent symptoms in childhood predicted which children with ADHD were at greatest risk for these outcomes.[44]

Bipolar disorder is another disorder commonly seen in children with ADHD. Studies have estimated that bipolar disorder co-occurs among 10% to 20% of children and adolescents with ADHD.[45-47] Longitudinal studies of hyperactive children indicate a similar prevalence in adulthood,[5,10,26] although another longitudinal study of children with ADHD reported higher rates into adolescence (12%).[48] In some cases, ADHD may be evidence of more severe bipolar disorder. For example, ADHD is more common in cases of childhood-onset bipolar disorder, which suggests that in some cases ADHD may signal an earlier onset, more chronic bipolar disorder.[48] Regarding anxiety disorders, longitudinal studies of hyperactive children do not report significant elevations in comorbid anxiety disorders.[5,10,26] However, anxiety disorders have been reported in 10% to 40% of clinic-referred children and adolescents with ADHD.[23,49-51] Overall, these studies demonstrate that comorbidity is typical among adolescents with ADHD and further complicates its clinical presentation in adolescence. In addition to concerns about prognosis, such comorbidities can easily complicate issues related to assessment.

Assessment of Adolescents With ADHD

An empirically-based assessment of ADHD typically includes structured clinical interviews, standardized questionnaires, and a review of records, all in the context of diagnostic criteria.[14,52] Cognitive test performance may provide additional value when differentiating ADHD subtypes.[53] Although there is diagnostic continuity of ADHD from childhood into adolescence,[13] assessing ADHD during adolescence needs to be considered in the context of complicating factors. One such factor involves comorbidity. Comorbidity is common in adolescents with ADHD, and conditions can co-occur with ADHD or can mimic ADHD symptoms. Regarding the latter, a diminished ability to concentrate can also be a symptom of a major depressive episode, distractibility and being overly talkative can also be symptoms of a manic or hypomanic episode, and restlessness and difficulty concentrating can be symptoms of generalized anxiety disorder or post-traumatic stress disorder.[54] Further, substance use can confound the assessment for ADHD, as alcohol and illicit drug use can create cognitive impairments that are also common in youth with ADHD.[55-57]

An additional factor that emerges in assessments of adolescent ADHD involves reporting source. In childhood ADHD assessments, parents and teachers are the typical reporters.[14] However, adolescents spend more time with peers and less time with parents. Further, in contrast to elementary school, adolescents have multiple teachers who spend less time with them during the school day and thus have fewer opportunities to observe their students’ behavior. Self-report methods can be incorporated into adolescent ADHD assessments as well; however, adolescents with ADHD have a tendency to underreport the severity of their symptoms,[7,58] which should be considered in any assessment. In adolescents with ADHD, concerns about the accuracy of self-report involve not only their account of ADHD symptoms, but of past delinquent behaviors as well. In one study, adolescents and young adults with ADHD were less likely than those without ADHD to report accurately on delinquent behaviors they engaged in 1 year earlier.[59] Such inaccurate reporting of behavior in ADHD is consistent with findings that persons with ADHD have a tendency toward a positive illusory bias view of their behavior[60] and with theories of ADHD that argue that problems with self-awareness emerge from working memory impairments.[61]

Developmental changes in the presentation of ADHD symptoms also have implications for self-report in the assessment of adolescents with ADHD. In particular, the decline in overt hyperactive symptoms into adolescence[7,19,21,22] makes inattentive symptoms more prominent. As a clinical observation, inattentive features common in ADHD may be experienced more subjectively (eg, daydreaming) than more overt hyperactive behaviors (eg, getting out of one’s seat at inappropriate times), thus making self-report more relevant in this age group.

Finally, the appropriateness of diagnostic criteria for ADHD complicates adolescent assessment. Specifically, the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, Text Revision [54] states that symptom onset must have occurred by age 7 to qualify for an ADHD diagnosis. However, studies addressing the empiric basis for this criterion have called it into question and recommend a revision to include childhood onset at or before age 12.[39,62-64] One study assessing the implications of this diagnostic revision in a large longitudinal sample found that the prevalence estimate, correlates, and risk factors of ADHD would not be affected if this new diagnostic criterion were adopted.[65] Thus, although following diagnostic criteria in adolescent ADHD assessments is recommended, incorporating these more recent findings may be crucial in making a diagnosis.

Treatment of ADHD in Adolescence

Relatively less research has been devoted to efficacious treatments for adolescents with ADHD compared with treatments for children with ADHD.[66] Despite diagnostic continuity, given the physical, social, and psychological changes that occur in adolescents with ADHD, it is somewhat difficult to simply extend childhood treatments to this group. ADHD treatments in this age group are likely to require more extensive and costly interventions. Further, treating adolescents is particularly challenging because they are less likely than children to receive mental health services in the first place.[67]

ADHD treatment is focused on symptom management and the reduction of downstream effects of unmanaged ADHD, such as school failure, automobile accidents, and peer rejection.[68] The more complex academic and social demands during adolescence require a management plan that addresses academic needs throughout the school day and into the evening, as well as weekday and weekend activities including driving, athletic and artistic endeavors, and family and peer relationships. Symptom management should be analogous to symptom management for any lifelong condition, such as nearsightedness, diabetes, or asthma. Such comparisons emphasize that ADHD is not the fault of the person with the disorder but rather a neurobiological condition, and making such comparisons may help the teen deal with any stigma associated with a psychiatric disorder.[69]

For children with ADHD, psychoeducation about ADHD, psychopharmacology (primarily stimulants), parent training in behavior management methods, classroom behavioral modification and academic interventions, and special educational placement are the most effective or promising interventions.[68] The empiric literature regarding extending these treatments into adolescence is much less prevalent, however. Thus, although treatment options for adolescent ADHD may be available, not all are equally effective and in many cases well-controlled studies are lacking. However, some treatments for adolescents with ADHD and their families do have empiric support, particularly pharmacotherapy and specific psychosocial treatment approaches.[68,70]

Although the stimulants and nonstimulants used for the treatment of ADHD can cause minor changes in blood pressure and heart rate, most analyses of studies of cardiac events and sudden death in children, youth, and adults with ADHD treated with stimulants have not found a higher incidence of these events in patients without preexisting structural cardiovascular conditions or a family history of sudden death.[71,72] Therefore, only routine assessment of cardiovascular function, similar to screening for participation in school sports, is recommended.

Current guidelines and consensus statements[71,72] do not recommend specialty cardiovascular screening (including routine electrocardiogram) before initiating treatment for ADHD, either with stimulants or nonstimulants. However, because these medications are known to cause small elevations in blood pressure and pulse (in the case of stimulants and atomoxetine) or hypotensive changes (in the case of the alpha-2 agonists), blood pressure and heart rate should be checked before treatment is started and should be monitored regularly at follow-up visits.


Stimulant medications. Stimulants and noradrenergic agonists are psychotropic treatments approved by the US Food and Drug Administration (FDA) for use in adolescents. Stimulants include methylphenidates and amphetamine compounds; these medications have a long-standing history in the treatment of ADHD and are considered the first-line therapies for ADHD.[73] The 2 classes of stimulants have slightly differing mechanisms of action. Whereas both block the reuptake of dopamine and norepinephrine into the presynaptic neuron and thereby increase neurotransmitter concentrations, amphetamine compounds also increase the release of dopamine from presynaptic cytoplasmic storage vesicles.[74]

Stimulants are effective in approximately 70% of adolescents with ADHD.[75-77] At least 7 randomized controlled trials have been conducted among adolescents with ADHD and all but one support the efficacy of stimulants for ADHD in adolescence.[74] Consistent with findings of diagnostic continuity of ADHD from childhood into adolescence, the efficacy of stimulants (specifically, methylphenidate) is largely equal from childhood into adolescence.[78] In a meta-analysis of children and adolescents comparing the efficacy of the methylphenidates and amphetamine compounds, amphetamine compounds had a small yet statistically significant advantage over a standard-release form of methylphenidate for parent and clinicians ratings of ADHD symptoms and global ratings (but not for teacher ratings).[79] Although stimulants are effective in acutely reducing ADHD symptoms, common medication side effects (eg, decreased appetite) have prompted consideration of other pharmacologic interventions.[80]

Nonstimulant medications. Noradrenergic agonists approved by the FDA for use in children and adolescents with ADHD include guanfacine extended release (XR), clonidine modified release (MR),[81] and atomoxetine. Although the precise mechanism of action for treating ADHD is unclear, these medications likely facilitate dopamine and noradrenaline neurotransmission thought to play a role in the pathophysiology of ADHD.[81,82]

In 2009, guanfacine XR was the first alpha-2 agent to be approved by the FDA for use in the treatment of ADHD in children and adolescents. According to one randomized controlled trial in children and adolescents with ADHD, guanfacine XR performed better than placebo in reducing teacher-rated ADHD symptoms but not parent-rated ADHD symptoms.[83] In several double-blind, placebo-controlled trials involving child and adolescent participants, guanfacine XR performed significantly better than placebo in reducing ADHD symptoms.[84,85] A 2-year, open-label, follow-up study of guanfacine XR in children and adolescents, with or without co-administration of stimulants, demonstrated continued efficacy as that seen in short-term randomized controlled trials.[86] Such findings emerged in a similar study,[87] although the attrition rate in both studies was greater than 75%, limiting generalizability.

Two randomized, double-blind, placebo-controlled studies evaluating the efficacy of clonidine MR in children and adolescents with ADHD have been conducted. One assessed clonidine MR as a monotherapy, and another studied it as an add-on agent in patients on a non-optimal stimulant drug regimen. In both trials, clonidine MR significantly reduced ADHD symptoms from baseline and was well tolerated.[88,89]

Atomoxetine is another noradrenergic agonist approved for use in adolescents with ADHD,[90-92] and it has comparable efficacy with methylphenidate in reducing core ADHD symptoms in children and adolescents.[93] In one randomized, placebo-controlled, dose-response study of atomoxetine in children and adolescents with ADHD, atomoxetine was consistently associated with a significant reduction of ADHD symptoms.[94] Social and family functioning also improved among those taking atomoxetine with statistically significant improvements in measures of ability to meet psychosocial role expectations and parental impact. In a randomized, placebo-controlled study of atomoxetine among children and adolescents with ADHD, atomoxetine-treated participant reductions in ADHD symptoms were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings.[95] Additional trials have demonstrated the efficacy and tolerability of this medication in children and adolescents with ADHD.[96-101] In addition, acute atomoxetine treatment appears to be equally effective and equally tolerated in children and adolescents.[102] Such findings suggest that pharmacologic differences in tolerability or ADHD symptom response are negligible between children and adolescents.

Treatment Discontinuation in Adolescence

When considering pharmacotherapy, one issue relevant to adolescents with ADHD involves treatment discontinuation. The prevalence of prescribing by general practitioners to adolescent patients with ADHD drops significantly.[103] Further, this decline is greater than the reported age-related decline in symptoms, indicating that treatment is prematurely discontinued in many cases when symptoms persist.[104] In one longitudinal study,[105] 48% of children between the ages of 9 and 15 had discontinued ADHD medication. Age was a significant moderator of medication adherence such that adolescents were less likely to continue their medication.[105] Thus, in addition to a need for continued research devoted to effective treatments for adolescents with ADHD,[66] unique barriers to treatment such as premature discontinuation need to be addressed.

Psychosocial Treatments

In terms of psychosocial treatments for adolescents with ADHD, the empiric literature is sparse compared with the literature on pharmacotherapy options. In addition, because of the many developmental and environmental changes that occur during the transition into adolescence, childhood treatments are not easily translated for this age group. Developmental changes with implications for treatment include that adolescents have a greater cognitive capacity for abstraction, they have more behavioral self-awareness, adolescents are undergoing identity formation and have a need for independence, there is peer influence, there is variability in daily school routines, and adolescents are undergoing physiologic changes (eg, development of secondary sex characteristics).[66] Thus, treatment approaches are recommended that include increased involvement of the teenager, behavioral contingencies that involve more opportunities to socialize with peers and exert independence, collaboration with multiple teachers, homework issues (particularly time management and organizational skills), and self-monitoring strategies.[44] Among studies that have considered psychosocial treatments for adolescents with ADHD, family-based and school-based approaches are the most promising.[44,106]

Family-Based Interventions

Three studies have examined family-based interventions. Barkley and colleagues[107] randomly assigned 12- to 18-year-olds to 8 to 10 sessions of behavior management training, problem-solving and communication training, or structural family therapy. All strategies resulted in significant improvement in negative communication, conflict, anger during conflicts, school adjustment, internalizing and externalizing symptoms, and maternal depressive symptoms at post-treatment, and improvements were largely maintained at a 3-month follow-up visit. However, only 5% to 20% in each treatment group demonstrated clinically significant reliable change following treatment.

Another study compared parent behavior management training with parent behavior management training/problem solving and communication therapy.[108] Both treatments resulted in significant improvement in parent-teen conflicts but were not statistically different from each other. Although such group-level analysis and normalization rates supported the efficacy of these treatments, reliable change indices were similar to those reported by Barkley and colleagues.[107]

Another study evaluated behavior management, problem solving, and education groups for parents of adolescents with ADHD.[109] Pretreatment and posttreatment comparisons indicated statistically significant reductions in the frequency and intensity of self-reported parent-adolescent conflict and in parent-reported problem behavior and positive effects on parent skills and confidence.

Although all these studies are promising, they did not produce much clinically significant reliable change or they were limited by methodologic design (ie, lack of a control or alternative treatment group). In terms of clinical implications, multimodal long-term treatment may be useful to assist parents in their interactions with their teens to manage parental and family distress,[110] as opposed to simply reducing ADHD symptom severity.

School-Based Interventions

Academic functioning is one of the most common concerns of parents of adolescents with ADHD.[110] Interventions targeting academic impairment in adolescents with ADHD are promising.[111] One school-based intervention involving directed note taking through group-based didactic and modeling yielded statistically significant improvements in on-task behavior, material comprehension, and daily assignment scores in a sample of adolescents with ADHD.[112] A more comprehensive treatment, called the Challenging Horizons Program,[113] involves after-school academic training incorporating behavioral strategies in a group and individual setting and monthly group parent training. This program has yielded moderate to large effect sizes on parent- and teacher-rated academic functioning and classroom disturbance compared with a community care group among middle school students with ADHD.[114] Although effect sizes were less promising for social functioning, and methodologic design limited the generalizability of these findings (eg, quasi-experimental design, small sample size), a 3-year treatment outcome study of this program indicated cumulative long-term benefits for the treatment group compared with a community care control group for parent ratings of ADHD symptoms and social functioning.[115] However, this latter study did not indicate any academic benefits of the treatment. Single-subject design studies also support the beneficial impact of behavioral techniques (eg, self-monitoring and functional analysis) in improving goal-oriented behavior in the classroom while reducing disruptive behavior among adolescents with ADHD.[116,117] This deserves additional consideration in future research.

A variant of the interventions aimed at academic behavior in adolescents with ADHD is also emerging. The Homework Intervention Program is a behavioral-based parent training program targeting homework in middle school students. In a pilot study of a small sample of middle school students diagnosed with ADHD (n = 11), multiple-baseline design analyses indicated an improvement in parent-reported homework problems and ADHD symptoms, overall grade point average, and teacher-reported productivity.[118]

Overall, comprehensive school-based interventions are promising and, similar to family-based interventions, warrant future research. Psychosocial treatment for adolescents with ADHD is a small, yet developing field of research. Current treatments need to be more thoroughly assessed. For example, social impairment continues into adolescence.[119] Further, social impairment in youth with ADHD increases the risk for substance use and related problems,[120] which demonstrates the need to also target social functioning in adolescent ADHD interventions. Providers also need to consider how to individualize treatment for adolescents with ADHD and the various potential comorbidities that can be present. In addition, treatments that complement existing psychosocial treatment approaches should be considered to target the multidimensional challenges that adolescents with ADHD face.[66] Some potentially complimentary treatments have yielded promising results. For example, attention training in cognitive training programs, mindfulness meditation, and physical exercise to reduce disruptive behaviors have shown potential, although more methodologically rigorous trials are required.[121-123]

Driving and ADHD

In North America, motor vehicle accidents are the leading cause of death among adolescents.[124] Drivers with ADHD are at significantly higher risk for poor driving outcomes, including increased traffic citations (particularly speeding), accidents that are their fault, repeated and more severe accidents, driving-related morbidity, and license suspensions and revocations.[125] Such findings were not better accounted for by comorbidity or intelligence. Given that substance use is not uncommon in persons with ADHD, the risks associated with drug and alcohol use should also be considered.[126] In terms of clinical implications of such findings, stimulant medications have been shown to improve driving performance in drivers with ADHD.[127-129] The method of stimulant delivery is also an important factor. In one study, adolescent drivers with ADHD drove better throughout the day on a driving simulator after taking an extended controlled-release stimulant compared with an immediate-release formulation.[126]

ADHD Pharmacotherapy and Growth

The effects of ADHD medication (especially stimulants) have been an area of considerable debate and controversy. Reviews indicate that treatment with stimulant medication does lead to subsequent delays in height (approximately 1 cm per year during the first 3 years of treatment) and weight.[130,131] These reviews also indicate that the effect of stimulants on growth decline over time, that growth deficits may be dose dependent, that growth suppression effects may not differ between methylphenidate and amphetamine, that stimulant discontinuation may lead to growth normalization, and that ADHD may itself be associated with dysregulated growth.[130,131]

In one longitudinal study, methylphenidate treatment was associated with small yet significant delays in height, weight, and body mass index.[132] Within the ADHD sample, those who had not received prior stimulant therapy and those who entered the study with an above average height, weight, and body mass index were most likely to experience growth deficits while taking stimulants. Further, the impact on all growth indices was most apparent during the first year of treatment and attenuated over time. In another longitudinal study that evaluated the effect of stimulant medication on physical growth, a newly medicated group exhibited reductions in size after 3 years of treatment relative to a nonmedicated group; the newly medicated group was 2.0 cm shorter and weighed 2.7 kg less.[133]

These findings indicate that in clinical settings, the potential benefits in symptom reduction and daily functioning need to be contrasted with the small but significant effects of pharmacotherapy (particularly stimulants) on growth. In most cases, growth suppression effects do not appear to be a clinical concern for most children treated with stimulants.[130] Although future studies are required to clarify the effects of continuous pharmacotherapy into adulthood to attain a better perspective of the long-term impact on growth, these findings suggest that growth rate should be monitored during treatment for ADHD.


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