Diagnoses of autism spectrum disorders vary widely across clinics

Archives of General Psychiatry study suggests common diagnostic subcategories like asperger syndrome are flawed and provides questionable value

NEW YORK (Nov. 9, 2011) -- To diagnose autism spectrum disorders, clinicians typically administer a variety of tests or scales and use information from observations and parent interviews to classify individuals into subcategories listed in standard psychiatric diagnostic manuals. This process of forming "best-estimate clinical diagnoses" has long been considered the gold standard, but a new study demonstrates that these diagnoses are widely variable across centers, suggesting that this may not be the best method for making diagnoses MHC Continuing Education

"Clinicians at one center may use a label like Asperger syndrome to describe a set of symptoms, while those at another center may use an entirely different label for the same symptoms. This is not a good way to make a diagnosis," says the study's lead investigator, Dr. Catherine Lord, director of the Institute for Brain Development, a partnership of Weill Cornell Medical College, NewYork-Presbyterian Hospital and Columbia University Medical Center. "Autism spectrum disorders are just that -- a spectrum of disorders. Instead of using subcategories, it would be better to simply report the results from agreed-upon tests and scales. This approach would provide more consistent and accurate information about individual patients."

The new study, published on Nov. 7 in the journal Archives of General Psychiatry, adds to previous evidence that standardized diagnostic instruments accurately predict who has autism and will continue to have it over time. It is also in line with recent skepticism about the value of categorical groupings of autism spectrum disorders in standard diagnostic manuals, such as the Diagnostic and Statistical Manual of Mental Disorders – IV – text revision (DSM-IV-TR) and the International Statistical Classification of Diseases. "There has been a lot of controversy about whether there should be separate diagnoses for autism spectrum disorder, especially Asperger syndrome," Dr. Lord says. "Most of the research has suggested that Asperger syndrome really isn't different from other autism spectrum disorders."

In the new study, Dr. Lord and co-author Dr. Eva Petkova, a biostatistician at NYU, studied about 2,100 people between the ages of 4 and 18 who were given a diagnosis of autism spectrum disorder by clinicians at 12 university-based centers. The participants were recruited from the Simons Simplex Collection, a multi-site project aimed at studying de novo genetic variations in families affected by autism spectrum disorders. The clinicians, who are experts in autism spectrum disorders, received training on how to administer and score the same set of cognitive tests and standardized instruments assessing social and communication skills and repetitive behavior, including the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview -- Revised (ADI-R). However, they received no specific training in making best-estimate clinical diagnoses. They used the DSM-IV-TR to classify individuals into three categories of varying severity: autistic disorder, pervasive developmental disorder -- not otherwise specified (PDD-NOS), and Asperger syndrome.

The researchers found that diagnoses of specific categories of autism spectrum disorder varied dramatically from site to site across the country. For instance, clinicians at one site gave only a diagnosis of autistic disorder, while clinicians at other sites gave that diagnosis to fewer than half of the participants. The proportion of individuals receiving a diagnosis of Asperger syndrome ranged from zero to nearly 21 percent across sites. These site differences were the second most important factor accounting for variation in the diagnoses (after social and communication deficits). However, the individuals with autism spectrum disorders did not vary significantly across sites in terms of their demographic information or developmental and behavioral characteristics, as measured by standardized instruments.

"The labels are pretty meaningless, because people are using the same general terms as if they mean the same thing, when they really don't," Dr. Lord says. "Because clinicians may not be using labels appropriately or diagnosing accurately, they may not be getting a sense of children's strengths and weaknesses and what therapy is best for them."

Clinicians across centers varied in how they weighed different factors and in the thresholds they set to make diagnoses. Although verbal IQ strongly influenced diagnoses at most centers, there were striking differences in the cutoff points used at each site to classify individuals into specific categories. The effect of age on diagnoses, and the specific age cutoff points, also varied dramatically across sites. "This doesn't make sense. You don't want to be told that you have a cold if you're 7 and a bacterial infection if you're 12, when you present with identical symptoms," Dr. Lord says.

The variability in clinical diagnoses could reflect regional differences, Dr. Lord says. For instance, services in some regions may be available only to children with a diagnosis of autistic disorder, but this same diagnosis may be stigmatizing or limit school options in other regions. Clinicians may also vary in how they take into account an individual's level of irritability and hyperactivity when judging the severity of autism spectrum disorder, Dr. Lord adds.

Because of the inconsistencies in best-estimate clinical diagnoses, the use of standard diagnostic manuals to classify individuals into subcategories of autism spectrum disorder should be reconsidered, Dr. Lord says. "It's very important for clinicians to use information from dimensions that directly relate to autism spectrum disorders, in addition to verbal IQ and the level of irritability and hyperactivity," she says. "The take-home message is that there really should be just a general category of autism spectrum disorder, and then clinicians should be able to describe a child's severity on these separate dimensions."

"This is an extremely important paper regarding our understanding of the various components of autism spectrum disorder from a group that has been crucial in defining the features of autism over many years," says Dr. Gerald D. Fischbach, scientific director of the Simons Foundation Autism Research Initiative. "They call attention to quantifiable traits rather than existing diagnostic categories. We are proud to have funded this project and to have gathered the Simons Simplex Collection on which this study is based under Dr. Lord's leadership."

In future research, Dr. Lord will work on improving diagnostic instruments --making them shorter, easier to use, and more appropriate for a wider variety of patients -- and assessing whether certain dimensions are really distinct from one another. This work will build on her previous pioneering efforts in developing these commonly used scales.


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Additional collaborating institutions include Columbia University Medical Center in New York City; the Simons Foundation in New York City; the University of Michigan in Ann Arbor; Emory University School of Medicine in Atlanta, Ga.; Emory University School of Medicine and Marcus Autism Center, Children's Healthcare of Atlanta, Ga.; Children's Hospital of Philadelphia in Pennsylvania; the University of Washington in Seattle; Vanderbilt University Medical Center in Nashville, Tenn.; Harvard Medical School in Boston, Mass.; the University of California, Los Angeles; Montreal Children's Hospital in Quebec, Canada; the University of Missouri in Columbia; Baylor College of Medicine in Houston, Texas; the University of Illinois at Chicago; Cincinnati Children's Hospital Medical Center in Ohio; the University of Minnesota in Minneapolis; and Indiana University in Bloomington.

This research was funded by the Simons Foundation and the National Institute of Mental Health.

Columbia University Medical Center


Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.

NewYork-Presbyterian Hospital


NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,409 beds. The Hospital has nearly 2 million inpatient and outpatient visits in a year, including 12,797 deliveries and 195,294 visits to its emergency departments. NewYork-Presbyterian's 6,144 affiliated physicians and 19,376 staff provide state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian Hospital/Westchester Division. One of the most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.

Weill Cornell Medical College


Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Older adults in home health care at elevated risk for unsafe meds

New study shows 40 percent of seniors cared for by a home health agency are taking a prescription that is potentially unsafe or ineffective to them

NEW YORK (Nov. 21, 2011) -- Older adults receiving home health care may be taking a drug that is unsafe or ineffective for someone their age. In fact, nearly 40 percent of seniors receiving medical care from a home health agency are taking at least one prescription medication that is considered potentially inappropriate to seniors, a new study in the Journal of General Internal Medicine has revealed LPC Ceus

The study's researchers, led by Dr. Yuhua Bao, assistant professor of public health at Weill Cornell Medical College, found that home health care patients aged 65 and over are prescribed Potentially Inappropriate Medications, or PIMs, at rates three times higher than patients who visit a medical office. The researchers' data shows that home health care patients are taking 11 medications on average, and that the concurrent use of multiple medications is a strong indicator of the presence of PIMs.

"Elderly patients receiving home health care are usually prescribed medications by a variety of physicians, and it's a great challenge for home health care nurses to deal with prescriptions from many sources," says Dr. Bao.

Still, she sees the home health care model offering potential for improving this situation. "Having a medical professional enter an elderly patient's home is an opportunity to do a proper medication review and reconciliation," Dr. Bao explains.

The study used data from the National Home and Hospice Care Survey, conducted in 2007 by the Centers for Disease Control and Prevention (CDC), which is the most recent nationally representative epidemiological survey of home health patients. The 2002 Beers Criteria, an expert-panel-generated list that itemizes 77 medications or groups of medications considered inappropriate for elderly people, was the basis for the PIMs chosen.

In a review of data of 3,124 home health patients 65 years of age or older, the researchers found 38 percent were taking at least one PIM. Senior patients taking 15 or more medications were five to six times as likely to be prescribed PIMs as patients taking seven or fewer medications. Of those seniors taking at least one PIM, 21 percent were taking 15 or more medications.

According to Dr. Bao, the study, if anything, underestimates the prevalence of PIMs taken by home health patients: The researchers were not able to look at potentially problematic drug-to-drug interactions or drug-and-disease interactions because data were not available.

There is no one reason why PIMs are prevalent in home health care settings. "Anecdotal evidence shows that many physicians are not aware of what is on the PIM list," says Dr. Bao. "In our fragmented health care system, we generally don't have an electronic reference for a patient that lists all medications from different physicians, and there isn't a readily available means for professionals to share essential information. Enhanced physician communication with home health care nurses may help to address the problem, as well as better communication among physicians."

Dr. Bao sees incentives for improvement in communication and care coordination in the implementation of the Patient Protection and Affordable Care Act passed by the U.S. Congress in 2010. "The current payment system doesn't provide incentives to optimize coordination of care," says Dr. Bao. "But when providers in different settings as a group are held responsible for outcomes and costs of care through, for example, an accountable care organization -- a concept promoted in the Affordable Care Act -- this could create an impetus to break the communication barriers that currently exist."


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Co-authors include Huibo Shao, Tara F. Bishop, Bruce R. Schackman and Martha L. Bruce -- all from Weill Cornell Medical College.

The study was funded by the National Institute of Mental Health. The authors do not have conflicts of interest.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Intervention Shows Promise in Treating Depression Among Preschoolers

Source: NIMH

A new psychosocial approach shows promise in helping preschoolers with symptoms of depression function better and learn to regulate their emotions, according to an NIMH-funded study published online ahead of print October 31, 2011, in the Journal of Child Psychology and Psychiatry.

Background

Recent studies have shown that symptoms of clinical depression can arise in children as young as 3, and may in fact be an early manifestation of a childhood mood disorder. However, no studies have investigated the best way to treat the disorder among children so young. In addition, many established psychosocial treatments for depression in adults and older youth, such as cognitive behavioral therapy or interpersonal therapy, might not be a good fit to the developmental needs of very young children.

Yet research has shown that very early behavioral interventions can have a significant impact on the trajectory of conduct problems and neuro-developmental disorders like autism or some developmental delays. These findings suggest that very early intervention for a mood disorder could potentially head off depression later in life lpc continuing education

Toward that end, Joan Luby, M.D., of Washington University and colleagues conducted a preliminary pilot study comparing a novel form of psychotherapy called Parent Child Interaction Therapy -Emotion Development (PCIT-ED) with a psycho-educational program. PCIT includes hands-on components aimed at strengthening the parent-child relationship by teaching positive play techniques and coaching parents through the process, and training parents in methods for handling noncompliance and disruptive behavior. PCIT has already been shown to be effective for treating disruptive disorders among preschoolers. The Emotion Development component was designed to help the parent enhance the child’s ability to recognize emotions in self and others and more effectively regulate intense emotions.

The psycho-education program—the control condition—educated parents in small groups about child development. It emphasized emotional and social development but did not include individual coaching or practice sessions with the parents and their children.

The researchers randomly assigned 54 preschoolers (aged 3-7) and their parents to either PCIT-ED or to the psycho-education program. Each program was conducted over a 12-week period.

Results of the Study

After 12 weeks, depression symptoms among the preschoolers significantly declined in both groups. The group receiving PCIT-ED also showed improvements in levels of anxiety, hyperactivity, conduct problems, hostility and inattention, whereas the group receiving the psycho-education program showed improvements in separation anxiety. In addition, the PCIT-ED group showed improvements in a child’s executive functioning and his or her ability to recognize and regulate emotions, compared to the control condition. The PCIT-ED group also reported reduced parenting stress and decreases in maternal depression, whereas the psycho-education group did not.

Significance

The results indicate that PCIT-ED is acceptable to families and may be beneficial. The researchers conclude that a full-scale randomized controlled trial is warranted.

What’s Next

While intriguing, the findings are preliminary only and should be interpreted with caution until further research can be conducted.

Reference

Luby J, Lenze S and Tillman R. A novel early intervention for preschool depression: findings from a pilot randomized controlled trial. Journal of Child Psychology and Psychiatry. Online ahead of print Oct. 31, 2011.

FOCUS ON TESTING HURTS STUDENTS IN HIGH SCHOOL HEALTH CLASSES

COLUMBUS, Ohio – High school health classes fail to help students refuse sexual advances or endorse safe sex habits when teachers focus primarily on testing knowledge, a new study reveals.

But when teachers emphasized learning the material for its own sake, and to improve health, students had much better responses. In these kinds of classrooms, students had lower intentions of having sex and felt better able to navigate sexual situations.

“A focus on tests doesn’t help students in health classes make healthier choices,” said Eric M. Anderman, lead author of the study and professor of educational psychology at Ohio State University.


Eric Anderman
“In health education, knowledge is not the most important outcome. What we really want to do is change behaviors, and testing is not the way to achieve that.”

The study appears online in the Journal of Research on Adolescence and will be published in a future print edition.

This study is part of a larger 5-year project that is studying HIV and pregnancy prevention in rural communities in Appalachia.

Researchers from Ohio State, the University of Kentucky and George Mason University are collecting data from more than 5,000 students in 32 Appalachian high schools.

For this study, students were surveyed in 9th grade before taking a health class that included information on HIV and pregnancy prevention. They were then surveyed again between four and six weeks after their class, and at the end of 10th grade, about one year later.

After taking the class, students were asked if their teachers had encouraged them to learn the material because they would be tested on it (called an extrinsic focus), or if the teachers encouraged them to truly learn and understand the information because it would be important for their lives (termed a mastery focus).

The researchers then compared these two groups of students on a variety of measures. Overall, the results showed that students in classes with a mastery focus were better off on a variety of health-related measures than were those whose teachers emphasized testing, Anderman said.

One example is the ability to refuse unwanted sexual advances. Findings showed that students in mastery classes reported they were better able to refuse sex 4 to 6 weeks later and even one year later than they were before the class began.

However, those in the extrinsic-focused classes “actually felt less effective at refusing sex after they took the class than they did before,” Anderman said.

Similar results were found when students were asked whether they thought they would wait to have sex.

Four to six weeks after the class, students whose teachers emphasized mastery were more likely to report that they wanted to wait to have sex, although there was no significant effect at a year later. That was not true for those who had extrinsic-focused classes, who were actually less likely to want to wait for sex after taking the class.

“That’s a really scary finding. The class was not having the intended effect when teachers emphasized the tests,” Anderman said.

Students were asked if their teachers had encouraged them to learn the material because they would be tested on it (called an extrinsic focus), or if the teachers encouraged them to truly learn and understand the information because it would be important for their lives (termed a mastery focus)ceus for counselors

Students in the mastery classes reported they felt better able to tell partners they would not have sex without using a condom at both time points after the class. Those in the extrinsic-oriented classes did not at the first follow-up.

Similar results favoring students in mastery-oriented classes occurred when students were asked about communication with parents about sex-related topics, knowledge about sex-related health issues, actual intentions to have sex, and belief about the importance of these health issues and whether they had the ability to learn more.

The results are clear, Anderman said.

“Focusing on knowledge about health does not equate to healthy behavior,” he said. “It’s more important for the students to improve their health than it is to get a 90 percent on a test.”

When students focus on tests, they are thinking about what they need to remember to get a good grade, he said. They are not taking the time to think about why they are learning this information, and why it is important in their life.

“Ideally, in the perfect world, I would say students shouldn’t be tested in health classes. Tests are important in a lot of areas, but health is not one of them,” he said.

“But if you have to have tests, make them minimal and low-pressure. This is not about separating students in terms of ability. It is about getting students to adopt healthy habits.”

Co-authors of the study were DeLeon Gray and Ann O’Connell of Ohio State; Pamela Cupp and Derek Lane of the University of Kentucky; and Rick Zimmerman of George Mason University.

The study was funded by a grant from the National Institute of Mental Health.

Widely Used Screening Tool Shown to Successfully Predict Suicide Attempts

A widely used suicide screening tool can help determine who is most at risk for suicide by pinpointing the threshold at which a person’s suicidal thinking is severe enough to warrant professional intervention, according to a recent study published online ahead of print November 8, 2011, in the American Journal of Psychiatry.

Background
Developing effective suicide prevention strategies is a priority of the Action Alliance for Suicide Prevention, a public-private partnership developed to advance the national strategy for suicide prevention. One of its main goals is to more efficiently identify those at risk so as to better target intervention. Standardized, reliable screening tools are needed to achieve that.
The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by a team of researchers from Columbia University, the University of Pennsylvania and the University of Pittsburgh to be used as part of the NIMH-funded Treatment of Adolescent Suicide Attempters (TASA) study. It was developed to meet the need for tracking changes in a person’s suicidal thinking and behavior over time, and to determine who is most at risk. The scale addresses the full range of suicidal behavior and thinking, but includes only the most essential, evidence-based items required for thorough assessment. The scale is now widely used for assessing suicidal thinking and behavior across research and practice in both psychiatric and non-psychiatric settings. It is used domestically and internationally by numerous stakeholders such as first responders (e.g., police, EMTs, fire departments), the U.S. Army, National Guards, prisons, hospitals, schools, and judicial systems to better identify those in need and to direct limited resources.

In this current analysis, Kelly Posner Ph.D., of Columbia University, and colleagues compared the C-SSRS to other similar measures, all of which were administered in three separate studies that featured teens who had attempted suicide or adults presenting to emergency rooms with psychiatric problems. They aimed to determine the scale’s validity, reliability and internal consistency, compared to the other measures.

Results of the Study

The researchers found that compared to other measures, the C-SSRS could reliably predict a potential suicide attempt in those who had previously attempted suicide. It also was able to determine clinically meaningful points at which a person may be at risk for an impending suicide attempt, something that other scales have been unable to consistently determine. According to the researchers, this type of predictive information can more precisely identify who needs the most help and when, while saving time and money by not having to refer people for treatment who are not at imminent risk.

Significance

This was the first major study showing how well the C-SSRS works with regard to identifying those most at risk for suicidal behavior. It was able to show, for the first time, that behaviors beyond previous suicide attempts—such as self-injury or making preparations for an attempt—may be used as predictors of subsequent suicide attempts.

What’s Next

Because the studies used in this analysis were not widely representative, additional research is needed to replicate the findings among diverse community samples counselor ceus

Reference

Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings from Three Multisite Studies with Adolescents and Adults. American Journal of Psychiatry. Online ahead of print Nov 8,2011.

NIH-funded study shows pre-birth brain growth problems linked to autism

Source: NIMH

Children with autism have more brain cells and heavier brains compared to typically developing children, according to researchers partly funded by the National Institutes of Health. Published in the Journal of the American Medical Association on Nov. 9, 2011, the small, preliminary study provides direct evidence for possible prenatal causes of autism.

"Earlier studies of head circumference and early brain overgrowth have pointed us in this direction, but there have been few quantitative neuroanatomical studies due to the lack of post-mortem tissue from children with autism," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of NIH. "These new results, along with an earlier study1 reporting altered wiring of the prefrontal cortex, focus our attention on this critical area of the brain in autism."

The prefrontal cortex is involved in various higher order functions such as language and communication, social behavior, mood, and attention. Children who have autism tend to show deficits in such functions.

Eric Courchesne, Ph.D., of the University of San Diego School of Medicine Autism Center of Excellence, and colleagues conducted direct counts of brain cells in specific regions of the prefrontal cortex in postmortem brains of seven boys who had autism and six typically developing males, ranging in age from 2-16 years. Most participants had died in accidents, but the researchers did not base their selection on causes of death.

To assist in this task, the researchers used a computerized tissue analysis system developed by co-investigator and NIMH grantee Peter Mouton, Ph.D., of the University of South Florida, Tampa, and colleagues.

The researchers found that children with autism had 67 percent more neurons in the prefrontal cortex and heavier brains for their age compared to typically developing children. Since these neurons are produced before birth, the study’s findings suggest that faulty prenatal cell birth or maintenance may be involved in the development of autism. Another possible factor that may contribute to the neuronal excess is a reduction in apoptosis, or programmed cell death, which normally occurs during the third trimester and early postnatal life.

Though small, this preliminary study examined all relevant postmortem tissue available at the time. The relative scarcity of tissue from very young children may limit future research as well, but efforts to include a larger number of samples are needed to confirm these findings and to identify patterns of age-related changes in autism.

This study was funded by Autism Speaks, Cure Autism Now, The Emch Foundation, the Simons Foundation, the Thursday Club Juniors, and the UCSD-NIH Autism Center of Excellence, which is supported by NIMH, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development continuing education for counselors

Reference
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K. Neuron Number and Size in Prefrontal Cortex of Children with Autism. JAMA. 2011 Nov 9;306(18).

1. Zikopoulos B, Barbas H. Changes in prefrontal axons may disrupt the network in autism. J Neurosci. 2010 Nov 3;30(44):14595-609. PubMed PMID: 21048117; PubMed Central PMCID: PMC3073590.

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Pitt team finds molecular evidence of brain changes in depressed females

PITTSBURGH, Sept. 16 – Researchers at the University of Pittsburgh School of Medicine have discovered molecular-level changes in the brains of women with major depressive disorder that link two hypotheses of the biological mechanisms that lead to the illness. Their results, published online this week in Molecular Psychiatry, also allowed them to recreate the changes in a mouse model that could enhance future research on depression.

Although women are twice as likely as men to develop depression and have more severe and frequent symptoms, very little research has focused on them or been conducted in other female animals, noted senior author Etienne Sibille, Ph.D., associate professor of psychiatry, Pitt School of Medicine.

"It seemed to us that if there were molecular changes in the depressed brain, we might be able to better identify them in samples that come from females," he said. "Indeed, our findings give us a better understanding of the biology of this common and often debilitating psychiatric illness."

The researchers examined post-mortem brain tissue samples of 21 women with depression and 21 similar women without a history of depression. Compared to their counterparts, the depressed women had a pattern of reduced expression of certain genes, including the one for brain-derived neurotrophic factor (BDNF), and of genes that are typically present in particular subtypes of brain cells, or neurons, that express the neurotransmitter gamma-aminobutyric acid (GABA.) These findings were observed in the amygdala, which is a brain region that is involved in sensing and expressing emotion.

In the next part of the project, the researchers tested mice engineered to carry different mutations in the BDNF gene to see its impact on the GABA cells. They found two mutations that led to the same deficit in the GABA subtype and that also mirrored other changes seen in the human depressed brain.

Dr. Sibille noted that researchers have long suspected that low levels of BDNF play a role in the development of depression, and that there also is a hypothesis that reduced GABA function is a key factor.

"Our work ties these two concepts together because we first show that BDNF is indeed low in depression and second that low BDNF can influence specific GABA cells in a way that reproduces the biological profile we have observed in the depressed brain," he said.

The team is continuing to explore the molecular pathway between BDNF and GABA and others that could be important in depression LPC CEUs


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Co-authors include Gaelle Douillard-Guilloux, Ph.D., Rama Kota, Ph.D., Xingbin Wang, Ph.D., George C. Tseng, Ph.D., and David Lewis, M.D., all of the University of Pittsburgh; Jean-Philippe Guilloux, Ph.D, of Pitt and Universite Paris-Sud; Alain Gardier, Ph.D., of Universite Paris-Sud; and, Keri Martinowich, of the National Institute of Mental Health, part of the National Institutes of Health.

The study was funded by the National Institute of Mental Health.



About the University of Pittsburgh School of Medicine


As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.