Smoking during pregnancy may increase risk of bipolar disorder in offspring

A study published today in the American Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children. Researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with scientists at the Kaiser Permanente Division of Research in Oakland, California, evaluated offspring from a large cohort of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring. Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood. "These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health. The authors wrote: "Much of the psychopathology associated with prenatal tobacco exposure clusters around the 'externalizing' spectrum, which includes attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and substance abuse disorders. Although not diagnostically classified along the externalizing spectrum, BD shares a number of clinical characteristics with these disorders, including inattention, irritability, loss of self-control, and proclivity to drug/alcohol use." In effect, children who were exposed to tobacco smoke in utero may exhibit some symptoms and behaviors that are found in BD. A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD LCSW Continuing Education ### Funding for the study was provided by the National Institute of Mental Health and the National Institute on Child Health and Development. The authors declare no financial or other conflicts of interest. About Columbia University's Mailman School of Public Health Founded in 1922, Columbia University's Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master's and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including the International Center for AIDS Care and Treatment Programs (ICAP), and the Center for Infection and Immunity. For more information, please visit http://www.mailman.columbia.edu Columbia University Department of Psychiatry & NYS Psychiatric Institute Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding and treatment of psychiatric disorders. It is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, BD and anxiety disorders, eating disorders, and childhood psychiatric disorders. Visit http://columbiapsychiatry.org/ for more information. Founded in 1959 by Jacob Yerushalmy at the University of California, Berkeley, The Child Health and Development Studies (CHDS) enrolled 15,000 families who were members of the Kaiser Permanente Medical Care Plan between 1959 and 1967. CHDS scientists discovered ways to make pregnancy safer for mothers and their babies. Now they are discovering connections between early life and cancer, heart disease, diabetes, fertility and mental illness. The National Institute of Child Health and Development of the National Institutes of Health makes this unique research possible through continuing support over 40 years. The CHDS is now a part of the Public Health Institute, Berkeley California. About the Kaiser Permanente Division of Research The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, the Division's 550+ staff are working on more than 350 ongoing research studies in behavioral health and aging, cancer, cardiovascular and metabolic conditions, health care delivery and policy, infectious diseases, vaccine safety and effectiveness, and women's and children's health.

New Data Reveal Extent of Genetic Overlap Between Major Mental Disorders

Schizophrenia, Bipolar Disorder Share the Most Common Genetic Variation Press Release • August 12, 2013 The largest genome-wide study of its kind has determined how much five major mental illnesses are traceable to the same common inherited genetic variations. Researchers funded in part by the National Institutes of Health found that the overlap was highest between schizophrenia and bipolar disorder; moderate for bipolar disorder and depression and for ADHD and depression; and low between schizophrenia and autism. Overall, common genetic variation accounted for 17-28 percent of risk for the illnesses. “Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher,” explained Naomi Wray, Ph.D., University of Queensland, Brisbane, Australia, who co-led the multi-site study by the Cross Disorders Group of the Psychiatric Genomics Consortium (PGC), which is supported by the NIH’s National Institute of Mental Health (NIMH). “Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses.” Dr. Wray, Kenneth Kendler, M.D., of Virginia Commonwealth University, Richmond, Jordan Smoller, M.D., of Massachusetts General Hospital, Boston, and other members of the PGC group report on their findings August 11, 2013, in the journal Nature Genetics. “Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature,” said Bruce Cuthbert, Ph.D., director of the NIMH Division of Adult Translational Research and Treatment Development and coordinator of the Institute’s Research Domain Criteria (RDoC) project, which is developing a mental disorders classification system for research based more on underlying causes. Earlier this year, PGC researchers – more than 300 scientists at 80 research centers in 20 countries – reported the first evidence of overlap between all five disorders. People with the disorders were more likely to have suspect variation at the same four chromosomal sites. But the extent of the overlap remained unclear. In the new study, they used the same genome-wide information and the largest data sets currently available to estimate the risk for the illnesses attributable to any of hundreds of thousands of sites of common variability in the genetic code across chromosomes. They looked for similarities in such genetic variation among several thousand people with each illness and compared them to controls – calculating the extent to which pairs of disorders are linked to the same genetic variants. The overlap in heritability attributable to common genetic variation was about 15 percent between schizophrenia and bipolar disorder, about 10 percent between bipolar disorder and depression, about 9 percent between schizophrenia and depression, and about 3 percent between schizophrenia and autism. The newfound molecular genetic evidence linking schizophrenia and depression, if replicated, could have important implications for diagnostics and research, say the researchers. They expected to see more overlap between ADHD and autism, but the modest schizophrenia-autism connection is consistent with other emerging evidence. The study results also attach numbers to molecular evidence documenting the importance of heritability traceable to common genetic variation in causing these five major mental illnesses. Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained – not to mention non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent. Similarly, the gaps are 25 percent vs. 75 percent for bipolar disorder, 28 percent vs. 75 percent for ADHD, 14 percent vs. 80 percent for autism, and 21 percent vs. 37 percent for depression. Among other types of genetic inheritance known to affect risk and not detected in this study are contributions from rare variants not associated with common sites of genetic variation. However, the researchers say that their results show clearly that more illness-linked common variants with small effects will be discovered with the greater statistical power that comes with larger sample sizes. “It is encouraging that the estimates of genetic contributions to mental disorders trace those from more traditional family and twin studies. The study points to a future of active gene discovery for mental disorders” said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch, which funds the project.

Common inherited genetic variation (single nucleotide polymorphisms, or SNPs) accounted for up to about 28 percent of the risk for some disorders, such as ADHD (dark green). Among pairs of disorders (light green), schizophrenia and bipolar disorder (SCZ-BPD) shared about 16 percent of the same common genetic variation (coheritabilities). Source: Cross-Disorder Group of the Psychiatric Genomics Consortium Professional Counselor Continuing Education Reference Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, August 11, 2013 Grants R01MH065562, R01MH43518, R01MH065554, R01MH65707, R01MH065571, R01MH65588, R01MH65578, R01MH65558 ### The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website. Press Contact(s) Jules Asher NIMH Press Office 301-443-4536 NIMHPress@nih.gov More Science News about: Attention Deficit Hyperactivity Disorder (ADHD) Autism Bipolar Disorder Depression Schizophrenia Contact the Press Office Phone: 301-443-4536 Email: NIMHpress@mail.nih.gov Press Resources Mental Health Information Statistics on Mental Disorders Summaries of Scientific Meetings Information about NIMH RePORTER: Research Portfolio Online Reporting Tool Expenditures and Results PubMed Central: An Archive of Life Sciences Journals Recommendations for Reporting on Suicide News from the Field News from the Field NIMH-Funded Science on EurekAlert Teen Eating Disorders Increase Suicide Risk The Love Hormone is 2-Faced Fear Factor: Missing Brain Enzyme Leads to Abnormal Levels of Fear in Mice, Reveals New Research More news from the field... Bookmark & Share Newsletters RSS Feeds Facebook

5 Most Common Mental Illnesses Share the Same Genes

From Autism to Depression: Largest Genetic Study Shows Mental Disorders Share Genetic Kinks --Associated Press Mental Illnesses Share Common DNA Roots, Study Finds --nbcnews.com An NIMH-funded study published online today in Lancet reveals that the five most common disorders—autism, attention deficit hyperactivity disorder, bipolar disease, schizophrenia, and major depression—all share similar genetic components. “These disorders that we thought of as quite different may not have such sharp boundaries,” said Dr. Jordan W. Smoller of Massachusetts General Hospital, one of the lead study authors. The results suggest that a rethink in how these disorders are defined might be in order. Rather than focusing on symptoms, which can be attributed to one or more disorder, physicians could one day start to rely on specific gene mutations or biologic pathways to make a formal diagnosis Aspira Continuing Education Online Courses And it also could lead to better treatments, said Dr. Bruce Cuthbert, director of the NIMH’s Division of Adult Translational Research and Treatment Development. “We are finally starting to make inroads where we have actual physiological mechanisms that we can target,” he said. “We can really start to understand the biology instead of having to guess at it.” Reference Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of Risk Loci with Shared Effects on Five Major Psychiatric Disorders: A Genome-wide Analysis. Lancet, published online February 28, 2013.

Rate of Bipolar Symptoms Among Teens Approaches That of Adults

The rate of bipolar symptoms among U.S. teens is nearly as high as the rate found among adults, according to NIMH-funded research published online ahead of print on May 7, 2012, in the Archives of General Psychiatry. Background Nationally representative data indicate that about 3.9 percent of adults meet criteria for bipolar disorder in their lifetime, and 2.6 percent meet criteria in a given year.1 However, limited data exist on the rates of bipolar disorder among adolescents, despite strong evidence indicating that bipolar disorder tends to emerge in adolescence or early adulthood. Kathleen Merikangas, Ph.D., of NIMH, and colleagues analyzed data from the NIMH-funded National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. Using criteria established by the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV), the researchers assessed teens for the hallmark symptoms of bipolar disorder—mania and depression. They also examined the rates of teens who showed evidence of mania alone. Results of the Study The researchers found that 2.5 percent of youth met criteria for bipolar disorder in their lifetime, and 2.2 percent met criteria within a given year. About 1.7 percent reported having mania alone within their lifetime, and 1.3 percent reporting having mania alone within a given year. Rates increased with age—about 2 percent of younger teens reported bipolar disorder symptoms, whereas 3.1 percent of older teens did. Significance The findings reveal that the prevalence of bipolar disorder in adolescents approaches that of adults, underscoring the widely held belief that the disorder first appears in youth. In addition, the presence of mania alone suggests that mania without depression should receive greater attention when evaluating mood disorders in teens, especially since it may precede or be associated with behavioral problems such as substance use disorders and attention deficit hyperactivity disorder, according to the researchers. What’s Next The researchers highlighted the need to follow up with these youth, to see if they continue to manifest bipolar symptoms as they age. More research is needed on the overlap of mania with other emotional and behavioral disorders, as well as the core features and risk factors for the development of mania in adolescents social worker continuing education Citation 1 Merikangas K, Cui L, Kattan G, Carlson G, Youngstrom E, Angst J. Mania with and without depression in a community sample of U.S. adolescents. Archives of General Psychiatry. Online ahead of print May 7, 2012.

Most Children with Rapidly Shifting Moods Don’t Have Bipolar Disorder

Relatively few children with rapidly shifting moods and high energy have bipolar disorder, though such symptoms are commonly associated with the disorder. Instead, most of these children have other types of mental disorders, according to an NIMH-funded study published online ahead of print in the Journal of Clinical Psychiatry on October 5, 2010. Background Some parents who take their child to a mental health clinic for assessment report that the child has rapid swings between emotions (usually anger, elation, and sadness) coupled with extremely high energy levels. Some researchers suggest that this is how mania—an important component of bipolar disorder—appears in children. How mania and bipolar disorder are defined in children is important because rapid mood swings and high energy are common among youth. Furthermore, many experts believe that overdiagnosis and misdiagnosis of bipolar disorder in youth may play a role in the increasing numbers of children being diagnosed with and treated for bipolar disorder. In choosing proper treatment, it is important to know whether children with rapid mood swings and high energy have an early or mild form of bipolar disorder, or instead have a different mental disorder CADC I & II Continuing Education In the Longitudinal Assessment of Manic Symptoms (LAMS) study, Robert Findling, M.D., of Case Western Reserve University, and colleagues assessed 707 children, ages 6-12, who were referred for mental health treatment. Of the participants, 621 were rated as having rapid swings between emotions and high energy levels, described as "elevated symptoms of mania" (ESM-positive). Parents of the other 86 children did not report rapid mood swings. These participants were deemed ESM-negative. Results of the Study At baseline, all but 14 participants had at least one mental disorder, and many had two or more. Attention deficit hyperactivity disorder (ADHD) was the most frequent diagnosis, affecting roughly 76 percent in both the ESM-positive and ESM-negative groups. However, only 39 percent were receiving treatment with a stimulant, the most common medication treatment for ADHD, at the start of the study. Only 11 percent of those with rapid mood swings and high energy (69 out of 621) and 6 percent of those without these symptoms (5 out of 86) had bipolar disorder, meaning that only this small percentage had ever experienced a manic episode, as defined by the current diagnostic system. Of the children with rapid mood swings and high energy, another 12 percent (75 children) had a form of bipolar disorder that includes much shorter manic episodes. Compared to children without rapid mood swings and high energy, those with these symptoms: Reported more symptoms of depression, anxiety, manic symptoms, and symptoms of ADHD Had lower functioning at home, school, or with peers Were more likely to have a disruptive behavior disorder (oppositional defiant disorder and/or conduct disorder). Significance Given that 75 percent of ESM-positive youth did not meet the diagnostic criteria for any bipolar disorder, the researchers suggest that bipolar disorder may not be common among children who experience rapid swings between emotions and high energy levels. Nevertheless, children with these symptoms experience significant impairments due to mood and behavior problems. The researchers also noted that ESM-positive and ESM-negative youth were prescribed psychotropic medications—including antipsychotics—at similar rates. Further study may provide insight into how serious mental illnesses should be treated in children. What's Next The study participants will be re-assessed every 6 months for up to 5 years, allowing the LAMS researchers to determine which children with rapid mood swings and high energy develop bipolar disorder later in life. Such research may inform efforts to identify early markers or predictors of the illness as well as possible protective factors. Reference Findling RL, Youngstrom EA, Fristad MA, Birmaher B, Kowatch RA, Arnold E, Frazier TW, Axelson D, Ryan N, Demeter CA, Gill MK, Fields B, Depew J, Kennedy SM, Marsh L, Rowles BM, Horwitz SM. Characteristics of Children With Elevated Symptoms of Mania: The Longitudinal Assessment of Manic Symptoms (LAMS) Study. J Clin Psychiatr. Epub 2010 Oct 5.