Autism early intervention found to normalize brain activity in children as young as 18 months

An intensive early intervention therapy that is effective for improving cognition and language skills among very young children with autism also normalizes their brain activity, decreases their autism symptoms and improves their social skills, a nationwide study has found. The researchers said the study is the first to demonstrate that an autism early intervention program can normalize brain activity. "We know that infant brains are quite malleable and previously demonstrated that this therapy capitalizes on the potential of learning that an infant brain has in order to limit autism's deleterious effects," said study author Sally Rogers, professor of psychiatry and behavioral sciences and a researcher with the UC Davis MIND Institute. "The findings on improved behavioral outcomes and the ability to normalize brain activity associated with social activities signify that there is tremendous potential for the brains of children with autism to develop and grow more normally," Rogers said. Published online today in the Journal of the American Academy of Child & Adolescent Psychiatry, the randomized, case-controlled, multi-centered study titled "Early behavioral intervention is associated with normalized brain activity in young children with autism," found that the children who received the intervention exhibited greater brain activation when viewing faces rather than objects, a response that was typical of the normal children in the study, and the opposite of the children with autism who received other intervention counselor ceus The U.S. Centers for Disease Control and Prevention estimates that 1 in 88 children born today will be diagnosed with autism spectrum disorder. Hallmarks of the neurodevelopmental condition include persistent deficits in social communication and relatedness, and repetitive or restrictive patterns of interest that appear in early childhood and impair everyday functioning. Named the Early Start Denver Model (ESDM), the intervention method was developed by Rogers and Geraldine Dawson, chief science officer of the research and advocacy organization Autism Speaks. The therapy fuses a play-based, developmental, relationship-based approach and the teaching methods of applied behavioral analysis. "This may be the first demonstration that a behavioral intervention for autism is associated with changes in brain function as well as positive changes in behavior," said Thomas R. Insel, director of the National Institute of Mental Health, which funded the study. "By studying changes in the neural response to faces, Dawson and her colleagues have identified a new target and a potential biomarker that can guide treatment development." For the present study, the researchers recruited 48 diverse male and female children diagnosed with autism between 18 and 30 months in Sacramento, Calif., and in Seattle, as well as typically developing case controls. The ratio of male-to-female participants was more than 3-to-1. Autism is five times more common among boys than girls. Approximately half of the children with autism were randomly assigned to receive the ESDM intervention for over two years. The participants received ESDM therapy for 20 hours each week, and their parents also were trained to deliver the treatment, a core feature of the intervention. The other participants with autism received similar amounts of various community-based interventions as well as evaluations, referrals, resource manuals and other reading materials. At the study's conclusion, the participants' brain activity was assessed using electroencephalograms (EEGs) that measured brain activation while viewing social stimuli -- faces -- and non-social stimuli -- toys. Earlier studies have found that typical infants and young children show increased brain activity when viewing social stimuli rather than objects, while children with autism show the opposite pattern. Twice as many of the children who received the ESDM intervention showed greater brain activation when viewing faces rather than when viewing objects -- a demonstration of normalized brain activity. Eleven of the 15 children who received the ESDM intervention, 73 percent, showed more brain activation when viewing faces than toys. Similarly, 12 of the 17 typically developing children, or 71 percent, showed the same pattern. But the majority -- 64 percent -- of the recipients of the community intervention showed the opposite, "autistic" pattern, i.e., greater response to toys than faces. Only 5 percent showed the brain activation of typical children. Further, the children receiving ESDM who had greater brain activity while viewing faces also had fewer social-pragmatic problems and improved social communication, including the ability to initiate interactions, make eye contact and imitate others, said MIND Institute researcher Rogers. Use of the ESDM intervention has been shown to improve cognition, language and daily living skills. A study published in 2009 found that ESDM recipients showed more than three times as much gain in IQ and language than the recipients of community interventions. "This is the first case-controlled study of an intensive early intervention that demonstrates both improvement of social skills and normalized brain activity resulting from intensive early intervention therapy," said Dawson, the study's lead author and professor of psychiatry at the University of North Carolina, Chapel Hill. "Given that the American Academy of Pediatrics recommends that all 18- and 24-month-old children be screened for autism, it is vital that we have effective therapies available for young children as soon as they are diagnosed." "For the first time," Dawson continued, "parents and practitioners have evidence that early intervention can alter the course of brain and behavioral development in young children. It is crucial that all children with autism have access to early intervention which can promote the most positive long-term outcomes." Rogers, Dawson and Laurie J. Vismara, also a researcher with the MIND Institute, have authored two books on the intervention. One for professionals is titled "Early Start Denver Model for Young Children with Autism: Promoting Language, Learning, and Engagement" and one for parents titled "An Early Start for Your Child with Autism: Using Everyday Activities to Help Kids Connect, Communicate, and Learn." The ESDM intervention is available in Sacramento through the MIND Institute clinic and in a number of locations throughout the U.S. and other nations. Training in delivering the ESDM method is provided through the MIND Institute and the University of Washington. ### Other study authors include Emily J.H. Jones, Kaitlin Venema, Rachel Lowy, Susan Faja, Dana Kamara, Michale Murias, Jessica Greenson, Jamie Winter, Milani Smith and Sara J. Webb, all of the University of Washington, and Kristen Merkle of Vanderbilt University. The study was funded by a grant from the National Institute of Mental Health and by a postdoctoral fellowship to Jones from Autism Speaks. Autism Speaks is the world's leading autism science and advocacy organization. It is dedicated to funding research into the causes, prevention, treatments and a cure for autism; increasing awareness of autism spectrum disorders; and advocating for the needs of individuals with autism and their families. At the UC Davis MIND Institute, world-renowned scientists engage in collaborative, interdisciplinary research to find the causes of and develop treatments and cures for autism, attention-deficit/hyperactivity disorder (ADHD), fragile X syndrome, 22q11.2 deletion syndrome, Down syndrome and other neurodevelopmental disorders. For more information, visit mindinstitute.ucdavis.edu

WSU researchers find the missing link between mental health disorders and chronic diseases in Iraq war refugees

October 15, 2012Subjects who fled Iraq after Gulf War were 43 times more likely to suffer from obstructive sleep apneaDETROIT – Wayne State University School of Medicine researchers may have discovered why people exposed to war are at increased risk to develop chronic problems like heart disease years later. And the culprit that links the two is surprising.Beginning in the mid-2000s, WSU researchers interviewed a random sample of 145 American immigrants who left Iraq before the 1991 Gulf War, and 205 who fled Iraq after the Gulf War began. All were residing in metropolitan Detroit at the time of the study. Study subjects were asked about socio-demographics, pre-migration trauma, how they rated their current health, physician-diagnosed and physician-treated obstructive sleep apnea, somatic disorders and psychosomatic disorders. Those who left Iraq after the war began and suffered from mental disorders such as post-traumatic stress disorder (PTSD) and depression, and self-rated their physical health as worse than their actual health, were 43 times more likely than pre-Gulf War immigrants to report obstructive sleep apnea (30.2 percent versus 0.7 percent) and later develop major chronic health issues such as cardiovascular disease.“I was surprised, but we had a specific theory we wanted to test. Changes in the stress system would contribute to sleep apnea. What happens? Maybe it’s the stress that leads to this fractured sleep,” said Bengt Arnetz, M.D., Ph.D., M.P.H., School of Medicine professor of occupational and environmental health, deputy director of the Institute of Environmental Health Sciences at Wayne State, and the study’s principal investigator and first author. “No one had explored this possible link before, although basic research suggests it as plausible.”The results are featured in the October 2012 issue of Psychosomatic Medicine, the peer-reviewed journal of the American Psychosomatic Society.According to the article, “Obstructive Sleep Apnea, Post-traumatic Stress Disorder, and Health in Immigrants,” obstructive sleep apnea occurs when the muscles supporting the soft palate at the back of the throat relax, but less is known about the reasons behind this neuromuscular malfunctioning.“It’s a known fact that the more exposure to violence you have, the more likely you are to report PTSD and depression, and the worse your self-rated health is, the more likely your actual health will suffer in five to 10 years,” Arnetz said.Hikmet Jamil, M.D., Ph.D., professor of occupational and environmental health in WSU’s School of Medicine, and Thomas Templin, Ph.D., research professor in WSU’s College of Nursing, also contributed to the article.The obstructive sleep apnea and chronic disase link has been observed among many trauma-exposed populations, including refugees, Arnetz said.“Iraqis were exposed to harsh conditions during the entirety of Saddam Hussein’s more than 20 years of reign. However, trauma and environmental exposures increased measurably and dramatically after the initiation of the 1991 Gulf War,” the article states.The study can now be used as a model for other populations, including U.S. soldiers returning home from battle.The multidisciplinary study brought together mental health research, sleep research and chronic disease research, Arnetz said.He and Jamil were partially supported by the National Institute of Mental Health of the National Institutes of Health (award number R01MH085793).To further test their ideas, the researchers plan to apply for funding from the National Institutes of Health to collaborate with Safwan Badr, M.D., professor and chief of the School of Medicine’s Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, and Thomas Roth, Ph.D., director of the Henry Ford Sleep Disorders and Research Center.###Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu.Founded in 1868, the Wayne State University School of Medicine is the largest single-campus medical school in the nation, with more than 1,000 medical students. In addition to undergraduate medical education, the school offers master’s degree, Ph.D. and M.D.-Ph.D. programs in 14 areas of basic science to about 400 students annually Professional Counselor Continuing Education

School-wide interventions improve student behavior

An analysis of a school behavior strategy—known as School-Wide Positive Behavioral Interventions and Supports (SWPBIS)—found that these types of programs significantly reduced children's aggressive behaviors and office discipline referrals, as well as improved problems with concentration and emotional regulation. The study, conducted by researchers from the Johns Hopkins Bloomberg School of Public Health, is the first randomized control trial to examine the impact of SWPBIS programs over multiple school years. The results were published October 15 in the journal Pediatrics as an eFirst publication.SWPBIS is a prevention strategy that aims to alter student behavior by setting universal, positively stated expectations for student behavior that are implemented across the entire school. Policies and decisions related to student behaviors are based on data analysis. SWPBIS programs are used in more than 16,000 schools in the U.S."These findings are very exciting, given the wide use of SWPBIS across the country. These results are among the first to document significant impacts of the program on children's problem behaviors, as well as positive behaviors, across multiple years as a result of SWPBIS," said Catherine P. Bradshaw, PhD, MEd, lead author of the study and associate professor in the Bloomberg School's Department of Mental Health.The randomized trial included a representative sample of 12,344 elementary school children from 37 schools. Approximately half of the students received free or reduced-priced meals, and nearly 13 percent received special education services. The researchers analyzed teachers' ratings of students' behavior and concentration problems, social-emotional functioning, pro-social behavior, office discipline referrals, and suspension over 4 school years.Overall, the study found significant improvement in children's behavior problems, concentration problems, social-emotional functioning, and pro-social behavior in schools using SWPBIS. Children in SWPBIS schools also were 33 percent less likely to receive an office discipline referral than those in the comparison schools. The effects tended to be strongest among children who were first exposed to SWPBIS in kindergarten."A unique feature of the model is the overall structure that is formed in schools to support sustainable services for students across a range of behavioral needs LCSW Continuing Education Using this framework, school staff can identify students at greatest need of services and efficiently target programs and resources to them," said Bradshaw.###The author of "Effects of School-Wide Positive Behavioral Interventions and Supports on Child Behavior Problems" include Catherine Bradshaw, PhD, MEd; Tracy E. Waasdorp, PhD, MEd; and Philip J. Leaf, PhD.

Many Teens Considering Suicide Do Not Receive Specialized Mental Health Care

HomeScience NewsScience News from 2012Science Update • October 12, 2012

Many Teens Considering Suicide Do Not Receive Specialized Mental Health Care

Source: iStockPhotoMost adolescents who are considering suicide or who have attempted suicide do not receive specialized mental health services, according to an analysis published online August 15, 2012, in Psychiatric Services, a journal of the American Psychiatric Association.

Background

National survey data from the Centers for Disease Control and Prevention (CDC) notes that approximately 14 percent of high school students seriously consider suicide each year, 11 percent have a suicide plan, and 6 percent attempt suicide. Other research has suggested that less than half of teens who attempt suicide received mental health services in the year prior to their attempt.Kathleen Merikangas, Ph.D., of NIMH and colleagues analyzed data from the National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. They asked teens whether they had any suicidal thoughts, plans, or actions (ideation) over a one-year period prior to the survey. They also completed a structured diagnostic interview regarding the full range of mental disorders including mood, anxiety, eating and anxiety disorders and whether they had received treatment for emotional or behavioral problems in the past 12 months. Respondents were asked to differentiate between receiving care from a mental health specialist such as a social worker, psychiatrist or other mental health professional, and receiving care from a general service provider, such as a primary care physician.

Results of the study

The survey revealed that, within the past year, 3.6 percent of adolescents had suicidal thoughts, but did not make a specific plan or suicide attempt. In addition, 0.6 percent reported having a plan, and 1.9 percent reported having made a suicide attempt within the past year.Suicidal behavior among youth was not only associated with major depression, but also with a range of other mental health problems including eating, anxiety, substance use and behavior disorders, as well as physical health problems. Between 50 and 75 percent of those teens who reported having suicidal ideation had recent contact with a service provider. However, most only had three or fewer visits, suggesting that treatment tends to be terminated prematurely. Moreover, most teens with suicidal ideation did not receive specialized mental health care.

Significance

The results of this study suggest that depression and other mood disorders are not the only pathways to suicide. They also highlight the importance of integrating risk assessment for suicide into routine physical and mental health care for teens. Even if adolescents are in treatment, they should continue to be monitored for suicidal ideation and behaviors, the researchers concluded.

Reference

Husky M, Olfson M, He J, Nock M, Swanson S, Merikangas K. Twelve-month suicidal symptoms and use of services among adolescents: results from the National Comorbidity Survey. Psychiatric Services in Advance, Aug 15, 2012. 

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Gene Variants Implicated in Extreme Weight Gain Associated with Antipsychotics

Gene Variants Implicated in Extreme Weight Gain Associated with Antipsychotics Source: JupiterExtreme weight gain associated with taking an antipsychotic medication may be linked to certain genetic variants, according to a study published in the September 2012 issue of the Archives of General Psychiatry. Background Antipsychotic medications, especially those known as “second generation” or “atypical” antipsychotics, generally are the first-line of treatment for schizophrenia and other serious mental disorders. They are effective in treating psychotic symptoms, but they are also associated with serious metabolic side effects that can result in substantial weight gain, and other cardiovascular problems.Some people appear to be more susceptible to severe weight gain than others, but it is difficult to predict who is most at risk. To date, there have been few genetic studies of weight gain associated with antipsychotics, in part because it is difficult to control such variables as prior exposure to the medications, and because patients often stop taking the medications prematurely.Anil Malhotra M.D., of the Feinstein Institute for Medical Research, and colleagues set out to identify any common gene variants associated with antipsychotic-induced weight gain in a group of patients who had never taken the medications before and who were carefully monitored to ensure they continued to take the medication over the study period. The initial study included a cohort of 139 pediatric patients who were prescribed a second-generation antipsychotic. Patients were examined over a period of 12 weeks to assess weight and metabolic effects of the medications.To compare and confirm their results, the researchers also conducted similar assessments of three small cohorts with adult patients taking second generation antipsychotics. Results of the Study The researchers found markers in a gene called the melanocortin 4 receptor (MC4R) that were associated with severe weight gain in people taking second generation antipsychotics. The MC4R region overlaps somewhat with another region previously identified as being associated with obesity in the general population. In addition, the results were replicated in the three independent cohorts. Significance In many genetic studies involving obesity, thousands of participants are needed to achieve statistically significant results and to overcome the many environmental factors that can influence a person’s weight. In this study, the critical environmental factor predisposing patients to weight gain was only antipsychotic medication use over a short period of time, thus allowing more control over other variables that could have confounded results. Therefore, even though the study only included 139 individuals, the researchers were able to detect results that implicated specific gene variants.The results also have potential clinical implications. Patients with the identified gene variants that would predispose them to severe weight gain while taking an antipsychotic could be directed to alternative treatments, especially those who do not have a psychotic disorder LPC Continuing Education Although particular gene variants were implicated, the study’s sample size was small. Further research with larger samples is needed to extend the findings. LPC CEUs Reference Malhotra A, et al. Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch Gen. Psychiatry. 2012 Sep. 69(9):904-912.

Medicare beneficiaries overspend by hundreds, Pitt Public Health finds

PITTSBURGH, Oct. 9, 2012 – Medicare beneficiaries are overpaying by hundreds of dollars annually because of difficulties selecting the ideal prescription drug plan for their medical needs, an investigation by University of Pittsburgh Graduate School of Public Health researchers reveals. Only 5.2 percent of beneficiaries chose the least-expensive Medicare prescription drug benefit (Part D) plan that satisfied their medical needs in 2009, overspending on Part D premiums and prescription drugs by an average of $368 a year. The evaluation, published in the October issue of the journal Health Affairs, takes a national look at how well beneficiaries were making plan choices in the fourth year of the Medicare Part D program and could help guide changes to health insurance programs. "People need assistance in choosing the least expensive plan for their medical needs," said lead author Chao Zhou, Ph.D., a post-doctoral associate at Pitt Public Health. "Educational programs that help people navigate the dozens of plans available would make it easier to select plans that best meet their health care needs without overspending." "In particular, government officials could recommend the three most appropriate Part D plans for each person, based on their medication history," said co-author Yuting Zhang, Ph.D., associate professor of health economics at Pitt Public Health. "Alternatively, they could assign beneficiaries to the best plan for them based on their medication needs, while offering them the option to choose another plan instead." The results of this study could be useful in designing health insurance exchanges, which are state-regulated organizations created under health care reform to offer standardized health care plans. "In designing health insurance exchanges, models with more active assistance would be more helpful than models with large numbers of plans and information," Dr. Zhang said. "For example, health insurance exchanges could actively screen plans on quality and negotiate premiums to reduce the number of plans." Implemented in 2006, Part D cost the federal government $65.8 billion in 2011, according to the Congressional Budget Office. The researchers looked at the difference in a patient's total spending, including the plan premium and out-of-pocket payment for the prescriptions filled, between the plan the patient chose and the cheapest alternative option in the region that would satisfy the patient's medication needs. The study looked at data for 412,712 people, with an average age of 75. Beneficiaries tend to overprotect themselves by purchasing plans with more generous features, such as generic drug coverage in the coverage gap. A few other trends emerged: As beneficiaries aged, they increasingly chose more expensive plans, with people older than 85 overspending by $30 more than people 65 to 69 years old. Blacks, Hispanics and Native Americans chose less expensive plans than whites. People with common medical conditions, such as diabetes and chronic heart failure, were not significantly more likely to choose more expensive plans. People with cognitive deficits or mental health issues, such as Alzheimer's disease, tended to choose less expensive plans, spending an average of $10 less than those without such conditions. The researchers could not determine if those people had assistance from caregivers. As the number of plan options increased in a region, the amount of overspending increased by $3.20 for every additional plan available. "A previous study showed that in 2006, beneficiaries could have saved nearly 31 percent of their total drug spending by switching to the lowest cost plan," Dr. Zhou said. "Since our results are similar, this suggests people are not learning to reduce overspending." One possible explanation for these consistent results over time is the impact of inertia and bias toward maintaining the status quo, she noted. "When Medicare Part D started in 2006, the majority of beneficiaries did not choose the least expensive plan," Dr. Zhou said. "Over time, they may have simply stuck to their original plan and never switched to a better one. Beneficiaries might not spend much time researching and adjusting their plan choices based on changes in their medication needs and in plan options." Findings from the private health insurance market support the authors' conclusion that people keep their current plan instead of spending time researching and optimizing their plan choices based on their insurance use and prescription spending in the previous year CADC I & II Continuing Education ### About the University of Pittsburgh Graduate School of Public Health The University of Pittsburgh Graduate School of Public Health, founded in 1948 and now one of the top-ranked schools of public health in the United States, conducts research on public health and medical care that improves the lives of millions of people around the world. Pitt Public Health is a leader in devising new methods to prevent and treat cardiovascular diseases, HIV/AIDS, cancer and other important public health problems. For more information about Pitt Public Health, visit the school's Web site at www.publichealth.pitt.edu. http://www.upmc.com/media

Researchers identify dozens of new de novo genetic mutations in schizophrenia

Many newly discovered genes most active during fetal development New York, NY (October 3, 2012) — Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease. The study, the largest and most comprehensive of its kind, was published today in the online edition of the journal Nature Genetics. Although schizophrenia typically onsets during adolescence and early adulthood, many of the mutations were found to affect genes with higher expression during early-to-mid fetal development. Together, the findings show that both the function of the mutated gene and when the gene is expressed are critically important in determining the risk for schizophrenia. The findings inform epidemiologic studies showing that environmental factors, such as malnutrition or infections during pregnancy, can contribute to the development of schizophrenia. "Our findings provide a mechanism that could explain how prenatal environmental insults during the first and second trimester of pregnancy increase one's risk for schizophrenia," said study leader Maria Karayiorgou, MD, professor of psychiatry at CUMC, and acting chief, division of Psychiatric and Medical Genetics, New York State Psychiatric Institute. "Patients with these mutations were much more likely to have had behavioral abnormalities, such as phobias and anxiety in childhood, as well as worse disease outcome." In an earlier study of 53 families, the team of investigators found that spontaneous, or de novo, mutations — genetic errors that are present in patients but not in their parents — play a role in a substantial portion of sporadic cases of schizophrenia. The mutations were found in the part of the genome that codes for proteins, known as the exome. In the larger, current study, the researchers performed whole-exome sequencing on 231 patient "trios" from the United States and South Africa. Each trio consisted of a patient and both of his or her parents, who were unaffected by the disease. By comparing the exomes of the patients with those of their parents, the researchers were able to identify de novo rather than heritable, mutations that may contribute to schizophrenia. This is the first study of this scale to search for single nucleotide variations in the exomes of schizophrenia patients. Previous studies from the Columbia group and others searched for much larger genetic variations, such as gene deletions or duplications. The researchers identified many mutated genes with diverse functions. They also identified four new genes (LAMA2, DPYD, TRRAP, and VPS39) affected by recurrent de novo events within or across the two populations, a finding unlikely to have occurred by chance. The researchers estimate that several hundred loci (genetic locations) can contribute to the development of schizophrenia. "The chance that two patients have exactly the same mutation or combination of mutations is rather small" said Dr. Karayiorgou. "What is intriguing is that despite this variability, people with schizophrenia tend to have, more or less, the same phenotype—that is, the same clinical presentation. Our hypothesis is that many neural circuits are extremely important in schizophrenia and that these circuits are vulnerable to a number of influences. So, when any of the genes involved in these circuits are mutated, the end result is the same." According to the researchers, the challenge remains to identify the affected biological processes and neural circuits, and to determine how they are affected. "Although the genetics of schizophrenia are extremely complex, a coherent picture of the disease is beginning to emerge," said co-director of the study Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center. "Our studies show that dozens, and perhaps hundreds, of different spontaneous mutations can raise one's risk for schizophrenia. On the surface, this is daunting, but using these new findings to understand how these mutations affect the same neural circuits, including during early fetal development, raises hopes that it may be possible to develop effective prevention and treatment strategies for the disease." Social Worker CEUs The paper is titled, "De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia." The other contributors are Bin Xu (CUMC), Iuliana Ionita-Laza (CUMC), J. Louw Roos (University of Pretoria, Pretoria, South Africa), Braden Boone (Hudson Alpha Institute for Biotechnology, Huntsville, Ala.), Scarlet Woodrick (CUMC), Yan Sun (CUMC) and Shawn Levy (Hudson Alpha Institute for Biotechnology). The research was partially supported by National Institute of Mental Health grants MH061399 and MH077235 and the Lieber Center for Schizophrenia Research at Columbia University. The authors declare no financial conflict of interest. About Schizophrenia Contrary to popular belief, schizophrenia is not a split personality; it is a chronic, severe, and disabling brain disorder that affects just over one percent of the adult population and is characterized by loss of contact with reality (psychosis), hallucinations (usually, hearing voices), firmly held false beliefs (delusions), abnormal thinking, a restricted range of emotions (flattened affect) or inappropriate and disorganized behavior, social withdrawal, and diminished motivation. The disease often strikes in the early adult years, and although many individuals experience some recovery, many others experience substantial and lifelong disability. People with schizophrenia often have problems functioning in society and in relationships and are over-represented on disability rolls and among the homeless and imprisoned. The precise causes of schizophrenia are not known, but current research suggests a combination of hereditary and environmental factors. Fundamentally, however, it is a biologic problem (involving changes in the brain), not one caused by poor parenting or a mentally unhealthy environment. Since the causes of schizophrenia are not clear, treatments focus on eliminating disease symptoms. Treatments include antipsychotic medications and various psychosocial treatments. ### 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 and 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 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. www.cumc.columbia.edu Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the Nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders. http://columbiapsychiatry.org/

For some women, genes may influence pressure to be thin

EAST LANSING, Mich. — Genetics may make some women more vulnerable to the pressure of being thin, a study led by Michigan State University researchers has found. From size-zero models to airbrushed film stars, thinness is portrayed as equaling beauty across Western culture, and it's an ideal often cited as a cause of eating disorder symptoms in young women. The researchers focused on the potential psychological impact of women buying into this perceived ideal of thinness, which they call thin-ideal internalization. Changes in self-perception and behavior, caused by this idealization, can lead to body dissatisfaction, a preoccupation with weight and other symptoms of eating disorders. "We're all bombarded daily with messages extoling the virtues of being thin, yet intriguingly only some women develop what we term thin-ideal internalization," said Jessica Suisman, lead author on the study and a researcher in MSU's Department of Psychology. "This suggests that genetic factors may make some women more susceptible to this pressure than others." To explore the role of genetic factors in whether women "buy in" to the pressure to be thin, the idealization of thinness was studied in sets of twins. More than 300 female twins from the MSU Twin Registry, ages 12-22, took part in the study. Suisman and colleagues measured how much participants wanted to look like people from movies, TV and magazines. Once the levels of thin idealization were assessed, identical twins who share 100 percent of their genes were compared with fraternal twins who share 50 percent. The results show that identical twins have closer levels of thin idealization than fraternal twins, which suggests a significant role for genetics. Further analysis shows that the heritability of thin idealization is 43 percent, meaning that almost half of the reason women differ in their idealization of thinness can be explained by differences in their genetic makeup. In addition to the role of genes, findings showed that influences of the environment are also important. The results showed that differences between twins' environments have a greater role in the development of thin ideal internalization than wider cultural attitudes, which women throughout Western societies are exposed to. "We were surprised to find that shared environmental factors, such as exposure to the same media, did not have as big an impact as expected," Suisman said. "Instead, non-shared factors that make co-twins different from each other had the greatest impact." Although the study did not look at specific environmental triggers, non-shared environmental influences typically include experiences that twins do not share with one another. This could include involvement by one twin in a weight-focused sport like dance, one twin being exposed to more media that promotes thinness than the other, or one of the twins having a friendship group that places importance on weight. "The take-home message," Suisman said, "is that the broad cultural risk factors that we thought were most influential in the development of thin-ideal internalization are not as important as genetic risk and environmental risk factors that are specific and unique to each twin." Kelly Klump, MSU professor of psychology and co-author on the study, said it is well established that a broad range of factors can contribute to the development of eating disorders LPC Continuing Education "This study reveals the need to take a similar approach to the ways in which women buy in to pressure to be thin, by considering how both genetic and environmental factors contribute to the development of thin-ideal internalization," Klump said. ### The study, funded by the National Institute of Mental Health, appears in the International Journal of Eating Disorders. Co-authors include Shannon O'Connor, Alexandra Burt and Cheryl Sisk from MSU; Steffanie Sperry and Kevin Thompson from the University of South Florida; Pamela Keel from Florida State University; Michael Neale from Virginia Commonwealth University; and Steven Boker from the University of Virginia.

Potential new class of drugs blocks nerve cell death

Potential new class of drugs protects nerve cells in models of Parkinson's disease and amyotrophic lateral sclerosis Diseases that progressively destroy nerve cells in the brain or spinal cord, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), are devastating conditions with no cures. Now, a team that includes a University of Iowa researcher has identified a new class of small molecules, called the P7C3 series, which block cell death in animal models of these forms of neurodegenerative disease. The P7C3 series could be a starting point for developing drugs that might help treat patients with these diseases. These findings are reported in two new studies published the week of Oct. 1 in PNAS Early Edition. "We believe that our strategy for identifying and testing these molecules in animal models of disease gives us a rational way to develop a new class of neuroprotective drugs, for which there is a great, unmet need," says Andrew Pieper, M.D., Ph.D., associate professor of psychiatry at the UI Carver College of Medicine, and senior author of the two studies. About six years ago, Pieper, then at the University of Texas Southwestern Medical Center, and his colleagues screened thousands of compounds in living mice in search of small, drug-like molecules that could boost production of neurons in a region of the brain called the hippocampus. They found one compound that appeared to be particularly successful and called it P7C3. "We were interested in the hippocampus because new neurons are born there every day. But, this neurogenesis is dampened by certain diseases and also by normal aging," Pieper explains. "We were looking for small drug-like molecules that might enhance production of new neurons and help maintain proper functioning in the hippocampus." However, when the researchers looked more closely at P7C3, they found that it worked by protecting the newborn neurons from cell death. That finding prompted them to ask whether P7C3 might also protect existing, mature neurons in other regions of the nervous system from dying as well, as occurs in neurodegenerative disease. Using mouse and worm models of PD and a mouse model of ALS, the research team has now shown that P7C3 and a related, more active compound, P7C3A20, do in fact potently protect the neurons that normally are destroyed by these diseases. Their studies also showed that protection of the neurons correlates with improvement of some disease symptoms, including maintaining normal movement in PD worms, and coordination and strength in ALS mice. Of mice and worms In the ALS mouse model, a highly active variant of the original P7C3 molecule, known as P7C3A20, which the investigators synthesized, largely prevented death of the nerve cells within the spinal cord that are normally destroyed by this disease. The P7C3 molecule also worked, but was not as effective at protecting neurons in this model. As cell survival increased in the ALS model, coordination and strength of the mice improved as well. Mice that were given P7C3A20 were able to stay on a rotating rod much longer than untreated animals or animals that received the less active compounds. Animals receiving P7C3A20 also performed better in analysis of their walking gait, which typically worsens in these animals as the disease progresses. In PD, dopamine-producing neurons necessary for normal movement are gradually destroyed. In patients, loss of these brain cells leads to tremors, stiffness, and difficulty walking. The study again showed that P7C3 protects these neurons from cell death and the more active analogue, P7C3A20, provided even greater protection. The two compounds also potently blocked cell death of dopaminergic neurons in a C. elegans worm model of PD. Moreover, reduced cell death in this model was associated with improved movement in the worms. Healthy C. elegans worms have a very characteristic swimming motion. This movement is disrupted in the PD worm. Hector De Jesus-Cortes, a graduate student of neuroscience at UT Southwestern Medical Center and lead author of the Parkinson's study, videotaped and analyzed the PD worms' mobility with and without treatment. Normal swimming was almost completely preserved with P7C3A20, and was also fairly well preserved with P7C3. Tweaking the molecule The research team compared the activity of several new P7C3-related compounds that they synthesized, in both the hippocampal neurogenesis screen and the mouse model of PD. "Every variation of our P7C3 molecule that works in the neurogenesis assay also works in the PD model," Pieper says. "As we continue to refine the molecule, our hope is that the results from the neurogenesis assay will accurately predict the neuroprotective potency of the compound, and thus aid in more rapidly optimizing a new neuroprotective agent." Nursing CEUs The team plans to continue tweaking the structure of the P7C3 molecule to improve its neuroprotective ability while eliminating potential side effects. "Our hope is that this work will form the basis for designing a neuroprotective drug that could eventually help patients," Pieper says. ### Pieper and De Jesus-Cortes conducted the study with colleagues at UT Southwestern Medical Center, including Steven McKnight, Ph.D., chairman of biochemistry, and Joseph Ready, Ph.D., professor of biochemistry. The work was funded in part by grants from the National Institute for Mental Health.