RI Hospital: Cognitive behavioral therapy benefits patients with body dysmorphic disorder

Patients reported considerable improvements in symptoms and disability PROVIDENCE, R.I. – In a recent study, researchers at Rhode Island Hospital found significant benefits of cognitive behavioral therapy as a treatment modality for patients with Body Dysmorphic Disorder (BDD). BDD is a common, often severe, and under-recognized body image disorder that affects an estimated 1.7 percent to 2.4 percent of the population. This study demonstrated significant improvement in patients' BDD symptoms and level of disability, as well as high levels of patient satisfaction with the treatment. The study is published online in advance of print in the journal Behavior Therapy. Researchers first developed the manualized treatment and then studied 36 adults with BDD who were randomly selected to either receive 22 cognitive behavioral therapy (CBT) sessions over 24 weeks, or placed on a 12-week wait list. Assessments were conducted pre-treatment, monthly, post-treatment and at three- and six-month follow-up appointments. Post-treatment, patients reported high satisfaction with the treatment, and BDD symptoms such as depression; insight regarding inaccurate beliefs about appearance; and disability in work, social life/leisure, and family life/home responsibilities significantly improved. "BDD is a common and often debilitating disorder, and there are very few proven effective treatments," said Katharine Phillips, M.D., director of the Body Dysmorphic Disorder program at Rhode Island Hospital, "This study suggests that using cognitive behavioral therapy that specifically targets BDD symptoms can result in significant improvements in symptoms and ability to function in daily life. We are currently conducting a study, funded by the National Institute of Mental Health, to more definitively test this treatment and compare it to the most commonly received type of therapy for BDD." CBT uses standard core elements relevant to all BDD patients, such as psychoeducation, cognitive interventions, exposure to avoided situations (which are usually social situations), and prevention of excessive repetitive behaviors (such as mirror checking or compulsive grooming). Treatment ends with relapse prevention strategies and booster sessions focused on helping patients maintain the gains they have made during treatment. Optional treatment modules focus on symptoms and behaviors that some, but not all, patients with this disorder engage in (such as compulsive skin picking or surgery seeking), which enables clinicians to tailor the treatment to individual patient needs. BDD typically starts during early adolescence. The disorder consists of intrusive, time-consuming preoccupations about perceived defects in one's physical appearance (for example, acne, hair loss, or nose size) whereas the perceived flaws are actually minimal or even nonexistent in the eyes of others. Individuals with BDD may engage in obsessive grooming, skin picking or plastic surgery (which appears to usually be ineffective). BDD also often leads to social impairments, missed work or school and difficulty forming and maintaining meaningful relationships. It is associated with high lifetime rates of psychiatric hospitalization and suicide. "Cognitive behavioral therapy is an often-helpful approach to treating BDD," Phillips said. "It can be tailored to meet the needs of a wide range of patients and includes unique strategies to address symptoms that distinguish BDD from other disorders." Phillips continued, "While more research is needed, we conclude from this study that CBT is an appropriate, feasible, and very promising alternative treatment for those suffering from this often misunderstood and severe mental illness." ### The study was funded in part by the National Institute of Mental Health (R34 MH070490). Phillips' principal affiliation is Rhode Island Hospital, a member hospital of the Lifespan health system in Rhode Island. She is also a member of the Department of Psychiatry and Human Behavior at The Warren Alpert Medical School of Brown University. Other researchers involved in the study were Elizabeth Didie of Rhode Island Hospital and the Alpert Medical School; and Sabine Wilhelm, Jeanne M. Fama, Jennifer L. Greenberg and Aparna Keshavia of Massachusetts General Hospital; Ulrike Buhlmann of the Institute of Psychology, Humboldt-Universität zu in Berlin, Germany; and Gail Steketee of Boston University. About Rhode Island Hospital Founded in 1863, Rhode Island Hospital in Providence, R.I., is a private, not-for-profit hospital and is the principal teaching hospital of The Warren Alpert Medical School of Brown University. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Last year, Rhode Island Hospital received more than $55 million in external research funding. It is also home to Hasbro Children's Hospital, the state's only facility dedicated to pediatric care. For more information on Rhode Island Hospital, visit http://www.rhodeislandhospital.org, follow us on Twitter @RIHospital or like us on Facebook http://www.facebook.com/rhodeislandhospitalpage. For more information on this and other mental health related topic, please visit MHC Continuing Education

Focusing on faces

Researchers find neurons in amygdala of autistic individuals have reduced sensitivity to eye region of others' faces Difficulties in social interaction are considered to be one of the behavioral hallmarks of autism spectrum disorders (ASDs). Previous studies have shown these difficulties to be related to differences in how the brains of autistic individuals process sensory information about faces. Now, a group of researchers led by California Institute of Technology (Caltech) neuroscientist Ralph Adolphs has made the first recordings of the firings of single neurons in the brains of autistic individuals, and has found specific neurons in a region called the amygdala that show reduced processing of the eye region of faces. Furthermore, the study found that these same neurons responded more to mouths than did the neurons seen in the control-group individuals. "We found that single brain cells in the amygdala of people with autism respond differently to faces in a way that explains many prior behavioral observations," says Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology at Caltech and coauthor of a study in the November 20 issue of Neuron that outlines the team's findings. "We believe this shows that abnormal functioning in the amygdala is a reason that people with autism process faces abnormally." The amygdala has long been known to be important for the processing of emotional reactions. To make recordings from this part of the brain, Adolphs and lead author Ueli Rutishauser, assistant professor in the departments of neurosurgery and neurology at Cedars-Sinai Medical Center and visiting associate in biology at Caltech, teamed up with Adam Mamelak, professor of neurosurgery and director of functional neurosurgery at Cedars-Sinai, and neurosurgeon Ian Ross at Huntington Memorial Hospital in Pasadena, California, to recruit patients with epilepsy who had electrodes implanted in their medial temporal lobes—the area of the brain where the amygdala is located—to help identify the origin of their seizures. Epileptic seizures are caused by a burst of abnormal electric activity in the brain, which the electrodes are designed to detect. It turns out that epilepsy and ASD sometimes go together, and so the researchers were able to identify two of the epilepsy patients who also had a diagnosis of ASD. By using the implanted electrodes to record the firings of individual neurons, the researchers were able to observe activity as participants looked at images of different facial regions, and then correlate the neuronal responses with the pictures. In the control group of epilepsy patients without autism, the neurons responded most strongly to the eye region of the face, whereas in the two ASD patients, the neurons responded most strongly to the mouth region. Moreover, the effect was present in only a specific subset of the neurons. In contrast, a different set of neurons showed the same response in both groups when whole faces were shown. "It was surprising to find such clear abnormalities at the level of single cells," explains Rutishauser. "We, like many others, had thought that the neurological abnormalities that contribute to autism were spread throughout the brain, and that it would be difficult to find highly specific correlates. Not only did we find highly specific abnormalities in single-cell responses, but only a certain subset of cells responded that way, while another set showed typical responses to faces. This specificity of these cell populations was surprising and is, in a way, very good news, because it suggests the existence of specific mechanisms for autism that we can potentially trace back to their genetic and environmental causes, and that one could imagine manipulating for targeted treatment." "We can now ask how these cells change their responses with treatments, how they correspond to similar cell populations in animal models of autism, and what genes this particular population of cells expresses," adds Adolphs. To validate their results, the researchers hope to identify and test additional subjects, which is a challenge because it is very hard to find people with autism who also have epilepsy and who have been implanted with electrodes in the amygdala for single-cell recordings, says Adolphs. "At the same time, we should think about how to change the responses of these neurons, and see if those modifications correlate with behavioral changes," he says MHC Continuing Education ### Funding for the research outlined in the Neuron paper, titled "Single-neuron correlates of abnormal face processing in autism," was provided by the Simons Foundation, the Gordon and Betty Moore Foundation, the Cedars-Sinai Medical Center, Autism Speaks, and the National Institute of Mental Health. Additional coauthors were Caltech postdoctoral scholar Oana Tudusciuc and graduate student Shuo Wang.

Bad boys: Research predicts whether boys will grow out of it -- or not

ANN ARBOR --- Using the hi-tech tools of a new field called neurogenetics and a few simple questions for parents, a University of Michigan researcher is beginning to understand which boys are simply being boys and which may be headed for trouble. “When young children lie or cheat or steal, parents naturally wonder if they’ll grow out of it,” says Luke Hyde, a U-M psychologist who is studying the development and treatment of antisocial behavior. Hyde, a faculty associate at the U-M Institute for Social Research (ISR) and assistant professor of psychology, is speaking at ISR on November 11 on how genes, experience and the brain work together to heighten or reduce the risks that normal childhood transgressions will develop into full-blown conduct disorders in adolescence and early adulthood. His talk is part of the ISR Research Center for Group Dynamics seminar series on violence and aggression, and is free and open to the public. “The lifetime prevalence of conduct disorder is around 10 percent, and even higher in males and low-income populations,” says Hyde. “The total cost to society is enormous, since these behaviors are often chronic, lasting through adulthood.” MHC Continuing Education With colleagues at U-M, Duke University, the University of Pittsburgh, and other institutions, Hyde has been exploring the role of the environment and biology as they interact over time to shape behavior. In particular, he is using the techniques of a new field called neurogenetics, which combines genetics, neuroscience and psychology, to learn how genes and neural processes interact with harsh environments, including dangerous neighborhoods and harsh parents, and with a child’s own levels of empathy and personality traits, to increase the risk of antisocial behavior. In one recent study, for example, Hyde and colleagues studied subjects with over-reactive amygdala responses . The amygdala is an almond-shaped part of the brain’s primitive limbic system involved in processing fear and other visceral emotions. It has been associated with impulsive, aggressive behavior, as well as anxiety disorders and depression. “Previous research suggests that the amygdala becomes over-reactive probably as a result of both genetics and experience,” says Hyde. “And once the amygdala is over-reactive, people tend to behave in an anxious, over-reactive way to things they see as a potential threat. “Our study found that this tendency is moderated by a person’s environment, including the social support they get. If they’re not getting support from family, friends, neighbors, or professionals, then the link between the amygdala and anxious behavior is much stronger.” In another study, Hyde and colleagues showed that kids who are impulsive are only at higher risk of engaging in antisocial behavior if they live in dangerous neighborhoods. He also identified specific items within childhood behavior checklists that can be used as early as the age of three to identify kids who will likely have worse trajectories for anti-social behavior compared to other children who have similar behavior problems, such as throwing tantrums. These items assess observable behaviors that include whether the child is cruel to animals, doesn’t seem to feel guilty after misbehaving, is sneaky, lies, is selfish or won’t share, and won’t change his or her behavior as a result of punishment. “The results of this test aren’t really meaningful until age three or three-and-a-half,” says Hyde. “Before that, many of these behaviors are fairly common, and don’t predict anything. But after age three, if children are still behaving in these ways, their behavior is more likely to escalate in the following years rather than improve.” There is good news, though. Kids who scored high on this test benefitted just as much as other kids from interventions, according to Hyde. These interventions, often called parent management training, focus on giving parents better skills to manage child behavior problems, including training parents to spend more positive time with their kids, use time-outs instead of physical punishments, and reward good behavior by giving out stickers. “Parents need to know that intervention works, especially if it’s done early,” says Hyde. “They need to go for help if they see signs of trouble. Clinical psychologists, among other professionals, have empirically supported treatments that are quite effective for children, especially in this age period.” ### Funding for this research was provided by The National Institute of Drug Abuse, the National Institute of Mental Health, and the National Heart, Lung and Blood Institute. Established in 1949, the University of Michigan Institute for Social Research (ISR) is the world's largest academic social science survey and research organization, and a world leader in developing and applying social science methodology, and educating researchers and students from around the world. For more information, visit the ISR Web site at http://home.isr.umich.edu

Simple tool may help evaluate risk for violence among patients with mental illness

Mental health professionals, who often are tasked with evaluating and managing the risk of violence by their patients, may benefit from a simple tool to more accurately make a risk assessment, according to a recent study conducted at the University of California, San Francisco. The research, led by psychiatrist Alan Teo, MD, when he was a UCSF medical resident, examined how accurate psychiatrists were at evaluating risk of violence by acutely ill patients admitted to psychiatric units. The first part of the study showed that inexperienced psychiatric residents performed no better than they would have by chance, whereas veteran psychiatrists were moderately successful in evaluating their patients' risk of violence. However, the second part of the study showed that when researchers applied the information from the "Historical, Clinical, Risk Management󈞀–Clinical" (HRC-20-C) scale – a brief, structured risk assessment tool – to the patients evaluated by residents, accuracy in identifying their potential for violence increased to a level nearly as high as the faculty psychiatrists', who had an average of 15 years more experience. "Similar to a checklist a pilot might use before takeoff, the HRC-20-C has just five items that any trained mental health professional can use to assess their patients," Teo said. "To improve the safety for staff and patients in high-risk settings, it is critical to teach budding psychiatrists and other mental health professionals how to use a practical tool such as this one." The study was published Aug. 31 in the journal Psychiatric Services. The HCR-20-C was developed several years ago by researchers in Canada, where it is used in a number of settings such as prisons and hospitals. However, in the United States, structured tools such as the HCR-20-C are only beginning to be used in hospitals. "This is the first study to compare the accuracy of risk assessments by senior psychiatrists to those completed by psychiatric residents," said senior author Dale McNiel, PhD, UCSF professor of clinical psychology. "It shows that clinicians with limited training and experience tend to be inaccurate in their risk assessments, and that structured methods such as HCR-20-C hold promise for improving training in risk assessment for violence." "The UCSF study was unusual," Teo added, "in applying a shorter version of the tool that could be more easily incorporated into clinical practice." Teo and his team assessed the doctors' accuracy by comparing the risk assessments that they made at the time patients were admitted to the hospital, to whether or not patients later became physically aggressive toward hospital staff members, such as by hitting, kicking or biting. The study included 151 patients who became violent and 150 patients who did not become violent mhc continuing education The patients in the study had severe mental illnesses, often schizophrenia, and had been involuntarily admitted to the hospital. ### The study was partly supported by the National Institute of Mental Health, a Minority Fellowship sponsored by the American Psychiatric Association and the Clinical and Translational Science Award from the National Institute of Health (NIH). When this study was conducted, all of the authors were affiliated with the UCSF Department of Psychiatry. Teo now is with the Department of Psychiatry, University of Michigan, Ann Arbor, and Sarah Holley, PhD, a co-author, now is with the Department of Psychology, San Francisco State University. Mark Leary, MD, of the UCSF Department of Psychiatry, also is a co-author. UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Daily or Severe Tantrums May Point to Mental Health Issues

Most young children lose their temper sometimes, but daily tantrums or tantrums with severe behaviors, such as aggressive or destructive tantrums, are unusual and could signal a larger problem, according to an NIMH-funded study published online August 3, 2012, in a special issue of the Journal of Child Psychology and Psychiatry. Background Distinguishing “normal” misbehaviors of early childhood from clinically worrisome problems can be challenging for pediatricians, parents, and others who work with young children. To address this issue, Lauren Wakschlag, Ph.D., of Northwestern University, Margaret Briggs-Gowan, Ph.D., of University of Connecticut Health Center, and their colleagues examined temper loss among preschoolers as a spectrum of behaviors ranging from mild or normal to “problem indicators” that may be signs of a greater, underlying mental health issue. For this study, the researchers developed the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB) questionnaire. Rather than merely asking whether a child had tantrums or not, the MAP-DB assesses the frequency, quality, and severity of behaviors related to temper tantrums and the extent of a child’s anger management skills over the past month. Parents of almost 1,500 preschoolers, ages 3-5, took part in the study. Results of the Study The researchers found that more than 80 percent of preschoolers had one or more tantrums in the past month. However, less than 10 percent had tantrums every day. Also, normal temper loss behaviors showed similar patterns and could be reliably distinguished from problem indicators. For example, over a one month period, tantrums typically occurred: when preschoolers were frustrated, angry, or upset (61 percent) during daily routines, such as bedtime, mealtime, or getting dressed (58 percent) with their parents (56 percent). In contrast, it was less typical for preschoolers to have a tantrum: with an adult who was not their parent, such as a babysitter or teacher (36 percent) during which they broke or destroyed things (28 percent) “out of the blue,” or for which parents could not discern a reason (26 percent) that lasted an unusually long time (26 percent) during which they hit, bit, or kicked someone else (24 percent). Significance The findings provide early evidence that studying behaviors as a spectrum may provide new insights into how mental disorders develop and better target early diagnosis, prevention, and treatment. “Our goal was to provide a standard method that would take the guesswork out of ‘when to worry’ about young children’s behavior and to provide a more developmentally sensitive way of characterizing the emergence of mental health problems, moving away from traditional approaches emphasizing extreme clinical distinctions to a dimensional approach that charts a progression from normal to abnormal,” said Wakschlag. What’s Next Further research is needed to confirm and evaluate the effectiveness of the MAP-DB questionnaire in identifying the point at which very young children would benefit from more specialized mental health screening and treatment. Changes in behavior as the child ages and whether problematic behaviors in early childhood lead to greater mental health issues later in life are also important areas for future study MHC Continuing Education Reference Wakschlag et al. Defining the developmental parameters of temper loss in early childhood: Implications for developmental psychopathology. Journal of Child Psychology and Psychiatry. In press. Related Funding: R01MH082830, R01MH090301

Studies seek better understanding and treatment of depression

AUGUSTA, Ga. – Connecting the dots between two molecules whose levels are decreased in depression and increased by current antidepressants could yield new therapies, researchers say. Serotonin is a neurotransmitter that enables brain cells to communicate and brain-derived neurotropic factor, or BDNF, is a brain-nourishing molecule that also aids connectivity. Popular antidepressants such as Prozac, developed to increase levels of serotonin, have recently been found to also increase BDNF levels, said Dr. Anilkumar Pillai, neuroscientist at the Medical College of Georgia at Georgia Health Sciences University. "We don't know how the molecule, serotonin, which is well-studied in depression, regulates BDNF signaling," Pillai said. He's principal investigator on a five year, $1.5 million grant from the National Institute of Mental Health to help him make the connection He suspects a critical piece is the protein transglutaminase 2, or TG2, expressed by brain cells and most other cell types. TG2 plays a role in natural serotonin recycling and potentially is a factor in the serotonin deficiency associated with depression. It also may help explain why levels of serotonin and BDNF seem to rise and fall in sync, Pillai said. TG2 coverts serotonin to Rac1, a protein that helps rejuvenate BDNF receptors, which typically sit on the surface of brain cells but must periodically move inside to reinvigorate. Depression appears to upset the balance of these complex, critical inner workings. Pillai hypothesizes that the high levels he has found in depression, likely result in too much serotonin conversion leaving too little of the neurotransmitter to properly support brain cell communication. Instead, more Rac1 is produced but – inexplicably – its degradation also increases ultimately decreasing BDNF signaling as well. Pillai has seen the unfortunate chain of events play out in an animal model with increased levels of TG2 and clear signs of depression. "If you can fix problems with the receptor, you should be able to reverse depressive symptoms in these mice," he said One of the many questions he wants to answer is whether existing antidepressants impact TG2. To help clarify the role of the impaired BDNF receptors, Pillai also wants to know whether giving BDNF to the depressed animal model improves depression. He's using a viral particle to directly activate the BDNF receptor. And he's also giving the TG2 inhibitor cysteamine to an animal model developed by administering stress hormones. He recently published in the journal PLoS ONE findings that the inhibitor appears effective in normalizing depressive behavior and BDNF levels in that model. Mental stress is a major factor in numerous psychiatric disorders including depression, schizophrenia and anxiety, he noted. Some antidepressants, such as Prozac, were designed to interfere with a natural recycling of serotonin called reuptake so more serotonin is available where needed to enable cell communication. Pillai said it's not yet clear if serotonin reuptake is the same thing as its conversion to Rac-1. "We need to learn more about how all these pieces fit to ultimately design new therapies for depression and related psychiatric disorders," he said. Dr. Alvin V. Terry Jr., MCG pharmacologist, is co-investigator on the studies MHC continuing education Major depressive disorder is the leading cause of disability in Americans age 15-44, affects about 14.8 million adults and is more prevalent in women, according to the National Institute of Mental Health. ###

Psychologists chase down sleep demons

What do Moby Dick, the Salem witch trials and alien abductions all have in common? They all circle back to sleep paralysis.

Less than 8 percent of the general population experiences sleep paralysis, but it is more frequent in two groups -- students and psychiatric patients -- according to a new study by psychologists at Penn State and the University of Pennsylvania.

Sleep paralysis is defined as "a discrete period of time during which voluntary muscle movement is inhibited, yet ocular and respiratory movements are intact," the researchers state in the current issue of Sleep Medicine Reviews. Hallucinations may also be present in these transitions to or from sleep.

Alien abductions and incubi and succubi, as well as other demons that attack while people are asleep, are implicated as different cultural interpretations of sleep paralysis. The Salem witch trials are now thought possibly to involve the townspeople experiencing sleep paralysis. And in the 19th-century novel Moby Dick, the main character Ishmael experiences an episode of sleep paralysis in the form of a malevolent presence in the room.

Brian A. Sharpless, clinical assistant professor of psychology and assistant director of the psychological clinic at Penn State, noted that some people who experience these episodes may regularly try to avoid going to sleep because of the unpleasant sensations they experience. But other people enjoy the sensations they feel during sleep paralysis.

"I realized that there were no real sleep paralysis prevalence rates available that were based on large and diverse samples," Sharpless said. "So I combined data from my previous study with 34 other studies in order to determine how common it was in different groups." MHC CEUs

He looked at a total of 35 published studies from the past 50 years to find lifetime sleep paralysis rates. These studies surveyed a total of 36,533 people. Overall he found that about one-fifth of these people experienced an episode at least once. Frequency of sleep paralysis ranged from once in a lifetime to every night.

When looking at specific groups, 28 percent of students reported experiencing sleep paralysis, while nearly 32 percent of psychiatric patients reported experiencing at least one episode. People with panic disorder were even more likely to experience sleep paralysis, and almost 35 percent of those surveyed reported experiencing these episodes. Sleep paralysis also appears to be more common in non-Caucasians.

"Sleep paralysis should be assessed more regularly and uniformly in order to determine its impact on individual functioning and better articulate its relation to other psychiatric and medical conditions," said Sharpless.

He looked at a broad range of samples, and papers were included from many different countries.

People experience three basic types of hallucinations during sleep paralysis -- the presence of an intruder, pressure on the chest sometimes accompanied by physical and/or sexual assault experiences and levitation or out-of-body experiences.

Up to this point there has been little research conducted on how to alleviate sleep paralysis or whether or not people experience episodes throughout their lives.

"I want to better understand how sleep paralysis affects people, as opposed to simply knowing that they experience it," said Sharpless. "I want to see how it impacts their lives." Sharpless hopes to look at relationships between sleep paralysis and post-traumatic stress disorder in the future.

This research was supported in part by the National Institute of Mental Health.

Also working on this research was Jacques P. Barber, professor of psychiatry, University of Pennsylvania.

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.

Same Behavior, Different Brain in Adolescent and Adult Rats

Science Update • January 28, 2011

Same Behavior, Different Brain in Adolescent and Adult Rats
A study that measured the activity of single cells in the brains of rats found striking differences between adolescents and adults even when both behaved identically on a task motivated by a reward. The finding offers clues to the neurological underpinnings of adolescent behavior and this age group's vulnerability to mental illness. MHC Continuing Education
Background
Numerous lines of research suggest that the adolescent brain, in both animals and humans, undergoes substantial change and maturation. By understanding of the nature of these changes scientists aim to clarify why mental illnesses like schizophrenia and mood disorders often have their first onset in adolescence and why rates of substance abuse and risky behavior is greater for this age group than others.

This Study
Researchers David Sturman and Bita Moghaddam at the University of Pittsburgh recorded the activity of single neurons in adolescent and adult rats as they worked for food rewards. The rats learned a very simple task—poking their nose into an illuminated hole—to receive a food reward. Such simple tasks are a building block for more complex behavior and make it possible to measure brain activity matched to action.

As the rats performed the task, investigators recorded the activity of single neurons in the orbitofrontal cortex, a part of the brain that is involved in the expectation of reward. Prior research has found that this part of the brain is not fully developed in adolescents. In this study, even when adult and adolescent rats behaved in exactly the same way in order to get the food reward, the pattern of firing of single cells in their brains was different. In comparison with adults, at key moments in the test—such as when they received the food reward—there was less inhibition of neuronal activity in the adolescents.

There were also differences in the levels of local electrical potentials which result from synchronized firing of groups of neurons. The levels of these potentials may reflect the capacity for coordinated firing of neurons across brain regions. The observed differences between adults and adolescents could be a reflection of less mature, less efficient connections in the brain in adolescents.

Significance
Brain activity represents an ongoing balance between excitatory and inhibitory activity. Earlier research has identified differences in brain activity between adults and adolescents; these investigators drilled down to the activity of single cells to try and identify the neural roots of differences in brain function linked to rewards; the first time scientists have done so in adolescents. The approach used in this work allowed them to watch how the adolescent brain responds to rewards resulting from behavior in real time.

The authors point out that inhibitory activity is important to the coordinated firing of neurons. The reduced inhibition they saw in adolescents suggests that they may respond more intensively than adults to reward. These more powerful responses may help explain the increased vulnerability of adolescents to the rewarding effects of alcohol and drugs. In addition, findings of differences in the regulation of neuronal firing observed in adolescents may ultimately help explain why schizophrenia—a disorder thought to represent an imbalance in inhibitory and excitatory activity in the brain—so often has its onset during adolescence and early adulthood. The exaggerated balance of excitatory and inhibitory activity in the brain observed in this work, superimposed on a genetically determined vulnerability to schizophrenia, might be a factor tipping someone towards illness. Monitoring how the adolescent brain processes events differently than the adult brain offers a powerful way to understand the vulnerabilities of young people at this age and develop means to intervene early.

Reference
Sturman, D.A. and Moghaddam, B. Reduced neuronal inhibition and coordination of adolescent prefrontal cortex during motivated behavior. Journal of Neuroscience 31:1471-1478, 2011.