Background
Childhood bipolar disorder is a relatively rare but seriously impairing condition. It is also associated with an increased risk of substance use disorders and suicide. To treat symptoms of mania, a key symptom of the disorder, medications such as mood stabilizers or antipsychotics are often prescribed. However, no prior study has addressed the question of which medication to try first.

In the Treatment of Early Age Mania (TEAM) study, Barbara Geller, M.D., of Washington University in St. Louis, and colleagues randomized 290 children ages 6-15 years diagnosed with bipolar I disorder (having mixed or manic symptoms) to treatment with lithium, divalproex sodium or risperidone for an 8-week trial. None of the children had taken an anti-manic medication before. Lithium has been used to treat bipolar disorder for many years. Divalproex sodium is an anticonvulsant mood stabilizer commonly prescribed to treat bipolar disorder as well. Risperidone is an atypical antipsychotic that has been approved by the U.S. Food and Drug Administration for the treatment of mania in youth age 10 and older.

Results of the Study
After eight weeks, 68.5 percent of the children taking risperidone showed improvement in manic symptoms, compared to 35.6 percent of those taking lithium and 24 percent of those taking divalproex sodium. Overall, 24.7 percent discontinued the trial, but more children taking lithium — 32.2 percent — discontinued the trial compared to those taking risperidone (15.7 percent discontinued) or divalproex sodium (26 percent discontinued.)

However, those taking risperidone also gained more weight than those on the other medications — an average of more than 7 lbs compared to around 3 lbs for those taking lithium and 3.7 lbs for those taking divalproex sodium. Those taking risperidone were also more likely to experience other metabolic side effects, such as an increase in cholesterol levels, compared to those on the other medications.

Significance
The researchers concluded that risperidone was significantly more effective than lithium or divalproex sodium for initial treatment of childhood mania. In addition, the children were less likely to discontinue the drug compared to those taking lithium or divalproex sodium, indicating a higher tolerance for it. This finding is consistent with other studies that have compared second-generation antipsychotics like risperidone to placebo in treating childhood mania.

However, the researchers caution that risperidone is associated with adverse metabolic effects that can increase the risk for diabetes and cardiovascular problems. They note that many children responded to low doses of the medication, suggesting that clinicians should be conservative when determining how to dose the medication. A lower dose may minimize the potential for serious side effects. The researchers also caution that because diagnostic measures for childhood bipolar disorder are not always consistent across studies, and because the validity of such a diagnosis in younger children is under debate, TEAM findings may not generalize to patients diagnosed using other measures.

What’s Next
More research is needed to develop safer, more effective interventions for children with early onset bipolar disorder for both initial and longer term treatment.

Material adapted from NIMH.

Reference
Geller B, Luby J, Josh P, Wagner KD, Emslie G, Walkup JT, Axelson DA, Bolhofner K, Robb A, Wolf DV, Riddle MA, Birmaher B, Ryan ND, Severe J, Vitiello B, Tillman R, Lavori P. A randomized controlled trial of risperidone, lithium and divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Archives of General Psychiatry. Online ahead of print January 2, 2012.

CNVs are genomic alterations in which there are too few or too many copies of sections of DNA. Researchers have known that spontaneously occurring (de novo) CNVs – genetic mutations not inherited from parents – significantly increase the risk for some neuropsychiatric conditions, such as schizophrenia or the autism spectrum disorders. But their role was unclear in bipolar disorder, previously known as manic depression.

Principal investigator Jonathan Sebat, PhD, assistant professor of psychiatry and cellular and molecular medicine at UC San Diego’s Institute of Genomic Medicine, and colleagues, found that de novo CNVs contribute significant genetic risk in about 5 percent of early onset bipolar disorder, which appears in childhood or early adulthood.

In other words, said the study’s first author Dheeraj Malhotra, assistant project scientist in Sebat’s lab, “having a de novo mutation increases the chances of having an earlier onset of disease.”

The cause or causes of bipolar disorder remain unclear. There is a clear genetic component – the disease runs in families – but previous studies that have focused mainly on common inherited variants have met with limited success in identifying key susceptibility genes.

Malhotra said that – while the findings do not conclusively pinpoint a specific gene or genomic region – the new findings show “convincing” evidence that rare copy number mutations strongly contribute to the development of early onset bipolar disorder. He added that sequencing of complete genomes or exomes of large number of bipolar families is needed to determine the total genetic contribution of all forms of de novo mutation to risk for bipolar disorder.

Funding for this research came, in part, from the National Institutes of Health, Ted and Vada Stanley, the Beyster family foundation, Wellcome Trust, Science Foundation Ireland, the Sidney R. Baer, Jr. Foundation and the Essel Foundation.

Co-authors of the study are Shane McCarthy, Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory; Jacob J. Michaelson, Beyster Center for Genomics of Psychiatric Diseases and UC San Diego Department of Psychiatry; Vladimir Vacic, Department of Computer Science, Columbia University and Stanley Institute for Cognitive Genomics; Katherine E. Burdick, Mount Sinai School of Medicine; Seungtai Yoon, Seaver Autism Center, Mount Sinai School of Medicine; Sven Cichon, Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn and Institute of Neuroscience and Medicine; Aiden Corvin and Michael Gill, Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Department of Psychiatry, Trinity College Dublin; Sydney Gary, Stanley Institute for Cognitive Genomics, Elliot S. Gershon, Department of Psychiatry and Behavioral Neuroscience, University of Chicago; Maria Karayiorgou, Department of Psychiatry, Columbia University; John R. Kelsoe, Department of Psychiatry and Institute for Genomic Medicine, UC San Diego; Olga Krastoshevsky, Verena Krause and Deborah L. Levy, Department of Psychiatry, McLean Hospital; Ellen Leibenluft, Section on Bipolar Spectrum Disorders, Emotion and Development Branch, NIMH; Vladimir Makarov, Seaver Autism Center and Stanley Institute for Cognitive Genomics; Abhishek Bhandari, Beyster Center for Genomics of Psychiatric Diseases, UC San Diego Department of Psychiatry and Stanley Institute for Cognitive Genomics; Anil K. Malhotra, Zucker Hillside Hospital; Francis J. McMahon, Genetic Basis of Moods and Anxiety Disorders, NIMH; Markus M. Nothen, Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn and German Center for Neurodegenerative Diseases; James B. Potash, Department of Psychiatry, University of Iowa, Marcella Rietschel, Central Institute of Mental Health, University of Heidelberg and Thomas G. Schulze, Department of Psychiatry and Psychotherapy, George-August University, Germany.

Material adapted from University of California, San Diego Health Sciences.

“Childbirth has an important influence on the onset and course of bipolar affective disorder, and studies have shown that episodes of post-partum psychosis are often best considered as presentations of bipolar affective disorder occurring at a time of dramatic psychological and physiological change,” the authors write as background information in the article. “It is also clear, however, that a high number of women with the new onset of a psychiatric disorder in the immediate post-partum period do not receive a diagnosis of bipolar disorder.”

Researchers collected data on 120,378 women born in Denmark from 1950 to 1991 who were alive in 2006 and had a history of a first-time psychiatric contact with any type of psychiatric disorder (admission or outpatient contact) with any type of psychiatric disorder excluding bipolar affective disorder. Each woman was followed up with individually from the day of discharge, with data collected on inpatient or outpatient psychiatric contacts during the follow-up period.

A total of 2,870 of these women had their initial psychiatric contact within the first year after delivery of their first child. During follow-up, 3,062 of the 120,378 women received diagnoses of bipolar affective disorder, of which 132 had their initial psychiatric contact 0 to 12 months post-partum. After adjusting for first diagnosis and family history of psychiatric illness, conversion rates to bipolar disorder were significantly predicted by the timing of initial psychiatric contact.

The authors found a significantly higher conversion rate to bipolar affective disorder in women having their initial contact within the first post-partum month. Additionally, the authors found evidence that the severity of the initial post-partum psychiatric episode may be important, as inpatient admissions were associated with a higher conversion rate than were outpatient contacts.

Fifteen years after initial contact, 13.87 percent of women with onset in the immediate post-partum period (0 to 30 days) had converted to bipolar disorder, 4.69 percent of women with later onset (31 to 365 days post-partum) and 4.04 percent of women with onset at other points had converted to bipolar disorder. Additionally, an extended analysis showed that 18.98 percent of women with onset in the immediate post-partum period had converted to bipolar disorder within 22 years after initial psychiatric contact. Conversely, 6.51 percent of women with later post-partum onset and 5.43 percent of women with onset at other points had converted to bipolar disorder after 22 years.

“The present study confirms the well-established link between childbirth and bipolar affective disorder and specifically adds to this field of research by demonstrating that initial psychiatric contact within the first 30 days post-partum significantly predicted conversion to bipolar affective disorder during the follow-up period,” the authors conclude. “Results indicate that the presentation of mental illness in the early post-partum period is a marker of possible underlying bipolarity.”

Material adapted from JAMA.

Reference
Arch Gen Psychiatry. Published online December 5, 2011. doi:10.1001/archgenpsychiatry.2011.157.

Researcher Marta Arrasate Gil

Her thesis, defended at the UPV/EHU, was entitled Valor predictivo de la sintomatología afectiva en primeros episodios psicóticos (Predictive value of affective symptomatology during the first psychotic episodes).

This is the first European PhD undertaken at the Álava/Araba Unit of the Faculty of Medicine of the UPV/EHU, and was codirected by Ana González-Pinto, 2010 National Award winner of the Spanish Society for Biological Psychiatry. According to Ms González-Pinto, the relevance of the research lies in that “affective symptoms can help not only in telling future prognosis but also in contributing to diagnosis – something difficult in psychiatry because diagnostic tests equivalent to a radiograph, an analysis or a scanner do not exist. This is why, if a test were found, however simple, or rudimentary, it would be of great use”.

Evaluation in three stages

Ms. Arrasate undertook the study based on a sample of 112 hospitalised patients with a first psychotic episode, and analysed the predictive value of the affective symptoms that present themselves in three concrete moments: initial hospital admission, the third year and the fifth year. In order to evaluate the results, the different affective symptoms were grouped according to dimensions (these classifications being based on a previous study of patients with bipolar disorders), and associated with variables such as the number of relapses, hospital or health centre admissions, suicide attempts, etc.

The results show that the activation dimension (involving symptoms of hyperactivity, lack of concentration and verborrhea, amongst others) can be an especially useful tool for early distinguishing between the various types of psychotic symptoms. This is what has been deduced from the data obtained from a study of one of the principal diseases in this field: bipolar disorder. According to Ms. Arrasate’s research, the activation and manic dimensions are those which best characterise bipolar disorder. Nevertheless, the manic dimension is often absent in the first episodes, while the depressive dimension is present during these first episodes, which possibly gives rise to confusion and inability in making an early and correct diagnosis. Thus, the results point to the activation dimension as the reliable path to follow: it is a useful predictive factor in the early diagnosis of bipolar disorder with psychotic symptoms.

These results open a new line of research as they prove that affective symptoms are able to discriminate between different psychoses, and contribute to an early diagnosis during its course. In fact, the evaluating panel for Ms. Arrasate’s thesis have made a point of informing those experts responsible for reviewing diagnostic criteria of mental diseases worldwide of these findings.

Material adapted from Elhuyar Fundazioa.

The new research comes as the Heinz C. Prechter Bipolar Research Fund, based at the U-M Depression Center, prepares to mark the 10th anniversary of its establishment by Waltraud “Wally” Prechter following the July 2001 death of her husband, Heinz. Before he took his life, few people knew that the well-known automotive entrepreneur wrestled with bipolar disorder.

“Currently the best treatments for bipolar disorder are only effective for 30 percent to 50 percent of patients,” says Melvin McInnis, M.D., the Thomas B and Nancy Upjohn Woodworth Professor of Bipolar Disorder and Depression at the U-M Medical School and associate director the U-M Depression Center. “New discoveries have been limited, in part due to the lack of access to tissue and cells from individuals with bipolar disorder. But that is now changing because of the Prechter research program and advances in stem cell research.”

The new stem cell lines – among the first to be created by the A. Alfred Taubman Medical Research Institute Consortium for Stem Cell Therapies – were made from fibroblasts from skin samples donated by adult research volunteers both with and without bipolar disorder.

In the lab, scientists can coax these skin cells into behaving like embryonic stem cells. Known as induced pluripotent stem cells, or iPSC, these, in turn, can be manipulated to develop into different types of body cells, including brain cells.

“We will be able to see if there are differences in how the neurons of a person with bipolar disorder make connections, determine how they respond to different medications and explore potential deficiencies in signaling pathways,” explains Sue O’Shea, Ph.D., a professor of cell and developmental biology at the Medical School who leads the stem cell lab with Gary Smith, Ph.D, professor of obstetrics and gynecology.

So far, five lines have been created. The goal, O’Shea says, is to develop 30 cell lines – 20 from people with bipolar disorder and 10 control subjects. Creating each line is a painstaking and expensive process.

“We often think of stems cells being used in therapies to treat disease, but this is a great example of stem cells’ usefulness for studying the mechanisms of disease,” O’Shea says. “The iPS cells renew themselves, so they’re an unlimited source of material and offer hope to individuals with bipolar disorder.”

Still, the researchers caution, new treatments spurred by this work could be a decade or more away.

Bipolar disorder, formerly known as manic depression, affects 5.7 million adults in the United States. It is caused by chemical imbalances in the brain and marked by significant changes in mood, thoughts, energy and behavior. Because bipolar disorder runs in families, research at U-M has focused on studying disease genes. There is no single gene that “causes” someone to become bipolar, but the disease has its roots in genetic vulnerabilities.

The Prechter Bipolar Genetic Repository already houses more than 1,500 genetic samples from people with bipolar disorder and healthy controls from studies at U-M along with collaborating sites: Johns Hopkins, Stanford, Cornell and Penn State. It is the first independently funded bipolar genetics repository in the nation. In addition to sharing the knowledge between the different universities, confidential, coded DNA repository samples and clinical information will be made available to scientists worldwide to accelerate and share clinical breakthroughs in evaluating and treating bipolar disorder.

The Prechter longitudinal study has already collected more than five years’ worth of data.

“I’m really proud that over the last 10 years my husband’s legacy has grown to include the strides we’re making to understand bipolar disorder and find new treatments,” Wally Prechter says. “Bipolar is like any other illness – cancer, diabetes, heart disease – and deserves the same urgency.”

That lack of effective treatment is a big reason for the high risk of suicide or suicide attempts among people with bipolar disorder, says McInnis. Anywhere from 5 percent to 15 percent of bipolar patients will attempt or commit suicide sometime in their lives.

Depression caused by Heinz Prechter’s bipolar disorder affected his whole being, Wally Prechter says.

“He was extremely exuberant and happy, and very, very optimistic, to the point that I thought, ‘Wow, I’ve never met anyone like that.’ But when he was depressed it was to the point that he would stay home and just sit in a chair and look out at the river,” she says.

The memory of how her brilliant husband was reduced to such a low, unable to tell anyone what he was going through, is part of what continues to drive her today.

U-M Health System CEO and Executive Vice President for Medical Affairs Ora Hirsch Pescovitz, M.D., points to the research as a great example of the strides that can be made when public institutions and private donors collaborate on research that benefits the public.

“The Prechter research shows how we continue to fuel innovation through exciting collaborations that highlight our commitment to bench-to-bedside medical advances,” Pescovitz says. “We are very fortunate to have Wally and her family as part of our Michigan family.”

Material adapted from University of Michigan.

The study was the first to look at sub-regions in the part of the brain known as the hippocampus. Abnormalities in the hippocampus are among the most consistent findings in schizophrenia research and are also implicated in bipolar disorder. Certain areas of the hippocampus (cornu ammonis regions 2 and 3) were found to be different, in terms of how their proteins are affected, in people with schizophrenia and bipolar disorder compared to the general population. The differences observed in these regions were found to be almost identical in both conditions.

A process which controls how information is transmitted by the shuttling of proteins to and from the synapse (a junction that permits a neuron to pass a signal to another cell) was also found to be is affected in both illnesses.

Professor David Cotter, Department of Psychiatry, RCSI and Beaumont Hospital commented: “Our study is the first to show the depth of protein similarities between schizophrenia and bipolar disorder as they appear in the brain and the processes associated with them. Although, the two conditions present with different symptoms, the research has shown that they are almost identical in terms of how they present in the brain,” Professor Cotter concluded.

Material adapted from Royal College of Surgeons in Ireland (RCSI).

Reference
Melanie Föcking, Patrick Dicker, Jane A. English, K. Oliver Schubert, Michael J. Dunn, David R. Cotter. Common Proteomic Changes in the Hippocampus in Schizophrenia and Bipolar Disorder and Particular Evidence for Involvement of Cornu Ammonis Regions 2 and 3. Archives of General Psychiatry. 68 (5): 477-88

Researcher June Gruber of Yale University

One of the characteristics of bipolar disorder is the extreme periods of positive mood, or mania. People in the grip of mania also have increased energy, sleep less, and experience extreme self-confidence. At first glance, this may sound good and even desirable. However, during these times of mania, people with bipolar disorder often take dangerous risks, run up their credit card debt, and wreak havoc in marriages. “The fact that positive emotion has gone awry is something unique about bipolar disorder, as almost all other emotional disorders are characterized by difficulties in negative emotions” Gruber says

Gruber points out that positive emotions are problematic for people with bipolar disorder even when they are not experiencing mania. Gruber has studied people whose bipolar disorder is in remission and found that they still experience more positive emotions than people who have never had bipolar disorder. More positive emotions may not sound like a bad thing, but there are times when these positive emotions are not appropriate.

“In our work, those with bipolar disorder continue to report greater positive emotions whether it’s a positive film, very sad film clip of a child crying over his father’s death, and even disgusting films involving someone digging through feces” she says. In more recent work Gruber and her colleagues have found they still feel good even if a close romantic partner tells them something sad face to face, they still feel good. “It’s rose-colored glasses gone too far.”

Clinical psychologists may also be able to use this research to figure out who with bipolar disorder is likely to relapse; people who have a lot of positive emotions, even at inappropriate times, may provide a window into possible early warning signs, Gruber says. This high level of positive emotion might even be used to predict who develops bipolar disorder. In a study of healthy college students who had never been diagnosed with bipolar disorder, Gruber found that those who showed these same high levels of positive emotions that persisted across positive, negative and neutral situations at higher risk for bipolar disorder.

But not all emotions are alike in bipolar disorder; in fact, they seem to have particular kinds of positive emotions. They report feeling more achievement and self-focused emotions like pride and rewarding feelings like joy. They do not differ social emotions that connect us with others, like love and compassion. “This mirrors early clinical observations and more recent scientific work,” Gruber says—that people with bipolar disorder set very high, ambitious goals, are sensitive to rewards, and in periods of mania, some believe they have special powers.

Psychologists should also consider that there are downsides of positive emotions even for people who do not have bipolar disorder, Gruber says. “Although positive emotions are generally good for us, when they take extreme forms or when they’re experienced in the wrong context, the benefits of positive emotion begin to unravel,” she says. The goal: “experience it in moderation, in the right place and time.”

Material adapted from Association for Psychological Science.

Two prior randomized controlled trials (RCTs) have shown the efficacy of STEPPS training. In both RCTs, patients with borderline features who did not meet strict DSM-IV criteria for BPD were excluded.

The authors of this study investigated the effectiveness of STEPPS in a sample representative of routine clinical practice and examined whether DSM-IV diagnosis and/or baseline severity were related to differential effectiveness. Patients whom their practicing clinician diagnosed with BPD were randomized to STEPPS plus adjunctive individual therapy (STEPPS, n=84) or to treatment as usual (n=84). STEPPS recipients showed more improvement on measures of general and BPD-specific psychopathology as well as quality of life than treatment as usual recipients, both at the end of treatment and at a 6-month follow-up.

Presence of DSM-IV-diagnosed BPD was not related to differential treatment effectiveness, but dimensional measures of symptom severity were; STEPPS was superior to treatment as usual, particularly in patients with higher baseline severity scores. The findings show the effectiveness of STEPPS in a ‘real-world’ sample, and underscore the importance of dimensional versus categorical measures of personality disturbance.

Material adapted from Journal of Psychotherapy and Psychosomatics.

Reference
Bos, E.H., van Wel, E.B., Appelo, M.T., & Verbraak, M.J.P.M. Effectiveness of Systems Training for Emotional Predictability and Problem Solving (STEPPS) for Borderline Personality Problems in a ‘Real-World’ Sample: Moderation by Diagnosis or Severity? Psychother Psychosom 2011;80:173-181.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center is one of 10 sites nationally participating in the CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness) study.

“Antipsychotic drugs have long been known to be useful for the treatment of bipolar disorder, but neurological side effects and toxicity have limited their long-term use. The good news is that the newer-generation antipsychotic drugs like quetiapine appear to be effective while having fewer neurological side effects,” says Dr. James H. Kocsis, site principal investigator, director of the Payne Whitney Affective Disorders Research Clinic at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and professor of psychiatry at Weill Cornell Medical College. “In this context, it is important that we compare the relative utility of the old-fashioned mood stabilizers like lithium and the newer second-generation antipsychotic drugs – with the ultimate goal of improving long-term treatment for patients with bipolar disorder.”

Researchers will follow 480 patients with bipolar disorder randomized to one of the two medications over a six-month period. Participants can continue taking other prescriptions, such as antidepressants, as long as they are not antipsychotic drugs. Often patients with bipolar disorder need three medications to feel well, explains Dr. Kocsis.

Bipolar disorder is a lifelong, chronic and highly recurrent mood disorder characterized by episodes of mania that alternate with episodes of major depression. Symptoms can negatively affect personal relationships, job or school performance, and may result in suicide.

The study is coordinated through the Massachusetts General Hospital (MGH) Bipolar Clinic and Research Program. The lead principal investigator is Dr. Andrew A. Nierenberg, director of the MGH Bipolar Research Program.

The AHRQ grant is part of an investment made under the American Recovery and Reinvestment Act of 2009, which designated $1.1 billion to support patient-centered outcomes research. This research is designed to inform health care decisions by providing evidence and information on the effectiveness, benefits and harms of different treatment options.

Prospective study participants can receive more information by calling Courtney Shelly at (212) 746-5705. For more information, patients may also call (866) NYP-NEWS.

Material adapted from New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College.

Problems with balance, postural control, and other motor control issues are frequently experienced by people with mood and psychiatric disorders, such as bipolar disorder and schizophrenia, and neurological disorders, such as Huntington’s and Parkinson’s disease, but research into the connections is scant.

If problems with postural control – maintaining balance while holding oneself upright – are a core component of bipolar disorder, as the study indicates, the researchers say it is possible that the motor abnormalities could appear before other symptoms, signaling an increased risk for the disorder.

It raises the question of whether therapies that improve motor symptoms may also help mood disorders, said Amanda R. Bolbecker, lead author.

“For a number of psychological disorders, many different psychiatric treatments and therapies have been tried with marginal effects over the long term. Researchers are really starting to look at new targets,” said Bolbecker, research scientist in the Department of Psychological and Brain Sciences in IU’s College of Arts and Sciences. “Our study suggests that brain areas traditionally believed to be responsible for motor behavior might represent therapeutic targets for bipolar disorder.”

Try as we might, humans cannot stand perfectly still. “Instead, we make small adjustments at our hips and ankles based on what our eyes, muscles, ligaments, tendons, and semi-circular canals tells us,” said S. Lee Hong, assistant professor in the Department of Kinesiology in IU’s School of Health, Physical Education and Recreation and a study co-author. “The better these sensory sources are integrated, the less someone sways.”

The study begins with the understanding that areas of the brain that are critical for motor control, mainly the cerebellum, basal ganglia and brain stem, also aid in mood regulation and are areas where abnormalities often are found in people with bipolar disorder. Postural sway – a measure of the degree of endless adjustments people make in an attempt to stand still – is considered a sensitive gauge of motor control that likely is affected by these abnormalities.

In the study, participants who had bipolar disorder displayed more postural sway, particularly when their eyes were closed, than study participants who had no psychological disorders. The troubles, which involved the study participants’ proprioception, or ability to process non-visual sensory information related to balance, were not affected by their mood or the severity of their disorder.

“It appears that people with bipolar disorder process sensory information differently and this is seen in their inability to adapt their movement patterns to different conditions, such as eyes open vs. eyes closed or feet together vs. feet apart,” said Hong, whose research focuses on how humans control motion. “The different conditions will cause people to use the information their senses provide differently, in order to allow them to maintain their balance.”

Bipolar disorder, formerly known as manic-depressive illness, is a severe psychiatric disorder characterized by extreme, debilitating mood swings and unusual shifts in a person’s energy and ability to function.

The study involved 16 people (seven women) with bipolar disorder and 16 age-matched people (nine women) who had no psychiatric disorders. They each stood barefoot and as still as possible on a piece of equipment called a force platform, which measured various aspects of postural sway as they stood with their eyes open and feet close together, eyes open and feet shoulder-width apart, eyes closed and feet together, and eyes closed and feet apart. The measurements during each 2-minute pose included such factors as the area covered by a person’s circular sway, how quickly they revolved and the degrees by which the sway moved more front to back or side to side.

Here are more findings from the study:

• The study is unique, the researchers say, because it does not suggest a “global motor deficit,” where people with bipolar disorder have movement problems all around. Instead, it suggests a specific problem adapting to changing sensory input – when people close their eyes, they rely on a different sources of sensory information, such as proprioception and the vestibular system.
• The study participants with bipolar disorder displayed a large decline in postural control when their eyes were closed, regardless of the position of their feet.
• A significant difference between the study groups involved their side-to-side postural control, which is largely a factor of the hips. The participants with bipolar disorder had less control. This difference was not seen in the front-to-back control, which relies on ankle adjustments. It is possible, the researchers wrote, that the participants with bipolar disorder might not have fully developed the control of posture using their hips, which is consistent with developmental factors contributing to bipolar disorder.

Research involving motor control, mood and psychiatric disorders is complicated by the fact that the primary treatment for these disorders is medication, which can have severe side effects including motor control problems. A limitation of Hong and Bolbecker’s study is that they could not factor out the effects of the various kinds and combinations of medications taken by their study participants with bipolar disorder.

The study was supported by NARSAD: the Brain and Behavior Research Fund, formally called the National Alliance for Research on Schizophrenia and Depression.

Coauthors include Jerillyn S. Kent, IU Department of Psychological and Brain Sciences; Mallory J. Klaunig, Larue D. Carter Memorial Hospital in Indianapolis; and Brian F. O’Donnell and William P. Hetrick, both of the Department of Psychological and Brain Sciences, Larue D. Carter Memorial Hospital and the IU School of Medicine.

Material adapted from Indiana University.

Download / Reference
Bolbecker AR, Hong SL, Kent JS, Klaunig MJ, O’Donnell BF, et al. 2011. Postural Control in Bipolar Disorder: Increased Sway Area and Decreased Dynamical Complexity. PLoS ONE 6(5): e19824. doi:10.1371/journal.pone.0019824

An experimental CBGT manual was developed and added to ‘treatment as usual,’ and results were compared with treatment as usual alone. Intention-to-treat analysis showed that there was no difference between groups in terms of time until any relapse (p = 0.414). When considering type of relapse, there was still no difference in either depressive (p = 0.068) or manic episodes (p = 0.221). Although occurrence of episodes also did not differ between groups (p = 0.59), median time to relapse was longer for patients treated with CBGT compared to the treatment as usual group (p = 0.011).

Time to recurrence and number of episodes were not different in the group of patients treated with CBGT. However, median time to relapse was shorter in the treatment as usual group. Studies with larger samples may help to clarify whether this CBGT approach prevents new episodes of bipolar disorder. These findings also indicated that CBGT is feasible in euthymic patients with bipolar disorder and should be investigated in future studies.

Material adapted from Journal of Psychotherapy and Psychosomatics

Reference
Gomes, B.C. ; Abreu, L.N. ; Brietzke, E. ; Caetano, S.C. ; Kleinman, A. ; Nery, F.G. ; Lafer, B. A Randomized Controlled Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder. Psychother Psychosom 2011;80:144-150.

“Previous research has shown that children of parents with bipolar disorder are four times as likely to develop mood disorders as those from parents without the condition,” says senior author Mark Ellenbogen, Canada Research Chair in Developmental Psychopathology at Concordia University and a member of the Centre for Research in Human Development. “The goal of our study was to determine how this is happening.”

Cortisol, the telltale hormone
Ellenbogen and colleagues had previously shown that cortisol levels in children with a parent affected by bipolar disorder were higher than kids whose parents were unaffected by the condition. The current study measured cortisol levels in these same individuals during chronic and episodic stress periods. In both circumstances, children of parents with bipolar disorder showed a greater increase in cortisol than those of parents without the disorder.

“Our study demonstrates that affected children are biologically more sensitive to the experience of stress in their natural and normal environment compared to unaffected peers,” says Ellenbogen. “This higher reactivity to stress might be one explanation of why these offspring end up developing disorders and is a clear risk factor to becoming ill later on.”

“We think we might be beginning to understand where we can intervene to actually prevent this increased sensitivity from developing,” continues Ellenbogen. “We believe this sensitivity develops during childhood and our suspicion is that if you could teach both parents and their offspring on how to cope with stress, how to deal with problems before they turn into larger significant stressors and difficulties, this would have a profound impact.”

About cortisol:
Cortisol is a hormone that is produced by the body in response to anxiety and researchers use cortisol to monitor the biological response to stress.

About bipolar disorder:
Bipolar disorder, which is also known as manic depression, is a treatable illness marked by extreme changes in mood, thought, energy and behavior. Bipolar disorder is also known as manic depression because a person’s mood can alternate between mania (highs) and depression (lows). These changes in mood, or “mood swings,” can last for hours, days, weeks or months.

Material adapted from Concordia University.

People with bipolar disorder are prone to extreme mood swings that take them from great emotional highs to the pits of depression; the cause of these mood swings is often put down to the patients’ genes and biology rather than their own thoughts and actions.

For this latest study – published in the American Psychological Association journal Psychological Assessment – the researchers followed 50 people with bipolar disorder for a month. The team found that the patients’ thinking and behaviour predicted their future mood swings even when their medical history had been accounted for.

“Individuals who believed extreme things about their moods – for example that their moods were completely out of their own control or that they had to keep active all the time to prevent becoming a failure – developed more mood problems in a month’s time,” said study lead Dr Warren Mansell, in Manchester’s School of Psychological Sciences.

“In contrast, people with bipolar disorder who could let their moods pass as a normal reaction to stress or knew they could manage their mood, faired well a month later. These findings are encouraging for talking therapies – such as CBT – that aim to help patients to talk about their moods and change their thinking about them.”

A new form of CBT, known as TEAMS (Think Effectively About Mood Swings), is being developed by Dr. Mansell and colleagues at The University of Manchester. It aims to improve on previous therapies by focusing on current problems like depression, anxiety, and irritability, and helping patients to set goals for their life as a whole.

The aim of this new approach is to encourage patients to accept and manage a range of normal emotions – like joy, anger and fear – and a controlled trial is about to start following a successful case series of the TEAMS approach.

The researchers will use the TEAMS approach to follow up their current findings with a larger study that identifies who relapses and who heads towards recovery in the long term.

Material adapted from University of Manchester.

Reference
‘Extreme Appraisals of Internal States and Bipolar Symptoms: The Hypomanic Attitudes and Positive Predictions Inventory,’ published in the ASA’s Psychological Assessment journal.

This study analyzed the factors associated to serious work, social, and family disabilities in a sample of 108 patients suffering from bipolar disorder.

This research revealed that work disability – that is, difficulty to perform normal job duties– in these patients was associated to high recurrence of maniac episodes, as well as to recurrent psychiatric hospitalization, high-intensity episodes, depression, and low educational levels. Furthermore, nicotinic dependency, a strong addiction to tobacco, can be more disabling in patients with bipolar disorder than depression.

Social support
Gutiérrez Rojas states that social disability – difficulty to establish relations out of the family and to achieve social integration – in these patients is associated to higher hospitalization rates, episodes of depression, and active depression symptoms. “Receiving social support is associated to lower social disability in these patients,” the author states.

Lastly, family disabilities, characterized by poor family relationships, was found to be associated to hospitalization, maniac episodes, symptoms of depression, and to higher scores in the CAGE scale, which measures addiction to alcohol.

The University of Granada researcher adds that to avoid disability in patients with bipolar disorder, “recurrence of depressive and maniac episodes must be avoided, and physicians should treat these episodes promptly to avoid hospitalization.”

Gutiérrez Rojas states that dependency on tobacco – apart from serious physical sequels – is associated to a worse bipolar disorder prognosis. Simultaneously, social support should be improved or sought for patients deprived of it. For instance, home assistance – instead of financial support – can be sought within the framework of the Spanish Law of Dependency. Patients can also be advised to attent patient meetings in search of information and support”.

Alcoholism is specially conflictive at family level, and alcohol is the most abused substance in patients with bipolar disorder. “Detecting alcohol abuse in patients is specially important to improve family relations.”

Material adapted from University of Granada.

Background
Although several studies report prevalence rates of mental disorders on an international level, the numbers have varied because each study tends to use different methodology and definitions. To remedy this, the World Health Organization’s World Mental Health (WMH) survey initiative used consistent data collection methods in 11 countries in the Americas, Europe, Asia, the Middle East and New Zealand. The survey also applied common diagnostic definitions for mental disorders found in the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV).

NIMH researcher Kathleen Merikangas, Ph.D., and colleagues used WMH data to track prevalence rates of three subtypes of bipolar spectrum disorder: bipolar I, bipolar II and bipolar disorder not otherwise specified (BD-NOS). Bipolar I disorder is considered the classic form of the illness in which a person experiences recurrent episodes of mania and depression. People with bipolar II disorder experience a milder form of mania called hypomania that alternates with depressive episodes. People with BD-NOS, sometimes called subthreshold bipolar disorder, have manic and depressive symptoms as well, but they do not meet strict criteria for any specific type of bipolar disorder noted in the DSM-IV. Yet, BD-NOS can significantly impair those who have it.

Results of the Study
The prevalence rates of bipolar I, bipolar II and BD-NOS were 0.6 percent, 0.4 percent, and 1.4 percent, respectively, with an overall bipolar spectrum rate of 2.4 percent. The United States had the highest prevalence rate of bipolar spectrum (4.4 percent), while India had the lowest rate (0.1 percent). More than half of those with bipolar disorder in adulthood note that their illness began in their adolescent years.

Across all countries studied, 75 percent of those who had bipolar symptoms met criteria for having at least one other disorder. Anxiety disorders, especially panic disorder, were the most common coexisting disorders, followed by behavior disorders and substance use disorders. Patterns of coexisting conditions were similar across countries.

Less than half of those with bipolar symptoms received mental health treatment. In low income countries, only 25 percent reported having contact with a mental health professional.

Significance
This study provides the first international prevalence data on bipolar disorder using reliable, standardized methodology. It highlights the international impact of bipolar disorder and the need for better recognition and treatment availability. The findings also support the notion that, given its multi-dimensional nature, bipolar disorder may be better characterized as a spectrum disorder.

In addition, because so many people note that their illness began in adolescence – a critical time of life for educational, occupational, and social development – early detection, intervention, and possibly prevention of subsequent coexisting disorders and complications should be emphasized.

What’s Next
More research is needed to better define the thresholds and boundaries of bipolar symptoms. In addition, further research is needed to better understand why and how the disorder tends to originate in adolescence and persist into adulthood, and how it intersects with coexisting mental disorders.

Material adapted from NIMH.

Reference
Merikangas KR, Jin R, He J, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Mora MEM, Browne MO, Ono Y, Posada-Villa J, Sagar R, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Archives of General Psychiatry. March 2011. 68(3):241-251.

In this film, we meet ‘Twink’, former photographer for The Jam, who has experienced the extremes of bipolar disorder for more than two decades. Twink is presently a patron of MDF The Bipolar Organisation and is passionate about helping Professor Nicholas Craddock, based at the Cardiff University School of Medicine, in his research to discover the underlying genetic factors that lead to this condition.

Professor Craddock, who is also featured in the film, was one of the main investigators in the Wellcome Trust Case Control Consortium study, in which around 2000 human genomes were studied for genetic hints to why certain people develop this mood disorder. He and his team continue to find and scrutinize the DNA of volunteers through the Bipolar Disorder Research Network, the largest study of bipolar disorder in the world, which is funded by the Wellcome Trust and the Stanley Medical Research Institute.

Material adapted from Welcome Trust.

In the past 15 years, as molecular mechanisms underlying the treatment of bipolar disorder began to emerge, basic research studies conducted in animals began to identify neuroprotective and perhaps neurotrophic effects of this important medication.

The identification of these molecular actions of lithium coincided with the discovery of regional brain volume deficits in imaging studies of people with bipolar disorder. In particular, a generation of research studies identified alterations, predominately reductions, in the size of brain regions involved in mood regulation. These studies also began to provide hints that some of the treatments for bipolar disorder would increase the volumes of these brain regions.

In a massive research effort published in Biological Psychiatry, eleven international research groups collaborated to pool brain imaging data from adults with bipolar disorder. This allowed them to perform a mega-analysis to evaluate the differences in brain structure between individuals with bipolar disorder and healthy comparison subjects.

They found that individuals with bipolar disorder had increased right lateral ventricular, left temporal lobe, and right putamen volumes. Individuals with bipolar disorder who were not taking lithium had a reduction in cerebral and hippocampal volumes compared with healthy comparison subjects.

Importantly, however, bipolar patients taking lithium displayed significantly increased hippocampal and amygdala volume compared with patients not treated with lithium and healthy comparison subjects. Cerebral volume reduction was also significantly associated with illness duration in bipolar individuals.

“This important mega-analysis provides strong support for regional brain structural alterations associated with bipolar disorder, but also sends a signal of hope that treatments for this disorder may reduce some of these deficits,” commented Dr. John Krystal, Editor of Biological Psychiatry.

Material adapted from Elsevier.

Reference / Abstract
The article is “Structural Magnetic Resonance Imaging in Bipolar Disorder: An International Collaborative Mega-Analysis of Individual Adult Patient Data” by Brian Hallahan, John Newell, Jair C. Soares, Paolo Brambilla, Stephen M. Strakowski, David E. Fleck, Tuula Kieseppä, Lori L. Altshuler, Alex Fornito, Gin S. Malhi, Andrew M. McIntosh, Deborah A. Yurgelun-Todd, Kevin S. Labar, Verinder Sharma, Glenda M. MacQueen, Robin M. Murray, and Colm McDonald. Please see the article for the authors’ affiliations and disclosures of financial and conflicts of interest. The article appears in Biological Psychiatry, Volume 69, Number 4 (February 15, 2011), published by Elsevier.

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.

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.

Material adapted from NIMH.

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.

“Prior research has consistently found associations between psychiatric conditions (e.g., depression, bipolar disorder, posttraumatic stress disorder [PTSD], schizophrenia and alcohol and/or drug use disorders) and risk of fatal and non-fatal suicide attempts,” the authors write. However, determining the association between individual psychiatric conditions and suicide risk has been difficult, in part because of the low numbers of suicides in many research studies.

The Veterans Affairs Healthcare System is the largest single healthcare system in the country, and recent research indicates veterans have an elevated risk of suicide when compared to the general population, the authors note. Mark A. Ilgen, Ph.D., and colleagues at the Department of Veterans Affairs (VA) Healthcare System and the University of Michigan, Ann Arbor, examined the associations between different types of psychiatric diagnoses and suicide risk among more than 3 million veterans who received any type of care at a VA facility in 1999 and were alive at the beginning of 2000. Psychiatric diagnoses were obtained from 1998 and 1999 treatment records and deaths by suicide were tracked over the following seven years.

During this follow-up period, 7,684 veterans died by suicide. Slightly less than half (46.8 percent) of those who died by suicide had at least one psychiatric diagnosis, and all of the psychiatric diagnoses examined – depression, schizophrenia, bipolar disorder, substance use disorders, PTSD and other anxiety disorders – were associated with an elevated risk of suicide.

“In men, the risk of suicide was greatest for those with bipolar disorder, followed by depression, substance use disorders, schizophrenia, other anxiety disorders and PTSD,” the authors write. “In women, the greatest risk of suicide was found in those with substance use disorders, followed by bipolar disorder, schizophrenia, depression, PTSD and other anxiety disorder.”

Overall, the least common diagnosis – bipolar disorder – was more strongly associated with suicide than any other condition. Bipolar disorder was diagnosed in 9 percent of those who died by suicide. “This makes bipolar disorder particularly appropriate for targeted intervention efforts or attempts to improve medication adherence,” the authors write.

“In all likelihood, many individuals with psychiatric disorders who were at risk for suicide were not identified by the treatment system,” the authors conclude. “This could be owing to stigma, which may have made individuals less likely to report their mental health symptoms to physicians, an effect that could be more pronounced among men with military experience. These findings highlight the importance of improved identification, diagnosis and treatment of psychiatric diagnoses (particular bipolar disorder, depression, substance use disorders and schizophrenia) of all health care system users.”

Material adapted from JAMA and Archives Journals.

Methodology
The study included 110 bipolar patients and 75 healthy controls (ages 18 to 65 years). Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology – self rating.

Principal Findings
Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients with the most prominent difficulties found in executive functioning (effect size [ES] = 0.49) and speed of information processing (ES = 0.47).

Total group (n = 110; dots), the euthymic subgroup (n = 46; triangle) and depressed subgroup (n = 64; square), with healthy controls (n = 75) used as reference score. Values are effect sizes, corrected for age. Error bars are 95% confidence intervals (95%CI). Statistical significance for group differences between bipolar patients and healthy controls was defined as p<0.05, shown in the figure as 95%CI which does not cross the base-line. Statistical significance (p<0.05) of sub-group differences were marked with an asterix (*) and were based on continuous depression scores. Speed = psychomotor speed; Process = speed of information processing; Attention = attentional switching; Verbal = verbal memory; Visual = visual memory; Exec/WM = executive functioning/working memory; Mean = mean z-score of all 6 cognitive domains.

Depressive symptoms were associated with dysfunction in psychomotor speed (r-squared [R²] = 7%), speed of information processing (R² = 20%), attentional switching (R² = 16%) and the mean score (R² = 24%), but not with verbal and visual memory and executive functioning.

Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains.

Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction.

Conclusions/Significance
Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.

Material adapted from PLoS ONE.

Download / Reference
van der Werf-Eldering MJ, Burger H, Holthausen EAE, Aleman A, & Nolen WA (2010). Cognitive Functioning in Patients with Bipolar Disorder: Association with Depressive Symptoms and Alcohol Use. PLoS ONE 5(9): e13032. doi:10.1371/journal.pone.0013032

Using functional magnetic resonance imaging, researchers at UIC examined the brain activity of children as they performed a working memory task while viewing faces with different emotions, such as angry, happy, or neutral expressions.

The children, ages 10 to 18, were asked to remember the faces and to press a button in the MRI-scanner if they saw the same face that was presented two trials earlier. The study involved 23 non-medicated children with bipolar disorder, 14 non-medicated children with ADHD, and 19 healthy controls.

“It’s a simple yet elegant working memory test that tells us a lot about how their brain remembers stimuli like faces or objects,” said Alessandra Passarotti, assistant professor of psychiatry at UIC and lead author of the study. “We also added in an emotional component – because both disorders show emotional deficits – to study how their working memory is affected by emotional challenge.”

The recent brain imaging study (Passarotti, Sweeney and Pavuluri, 2010) was the first to differentiate brain dysfunction in adolescents with pediatric bipolar disorder (PBD) and attention-deficit hyperactivity disorder (ADHD) during an affective working memory task with emotional challenge. While relative to healthy peers both the PBD and ADHD group exhibited working memory deficits and dysfunction of the dorsal and ventral prefrontal cortex, important brain regions specialized for working memory and emotion regulation, the ADHD group exhibited the most severe dysfunction. Moreover, PBD relative to ADHD exhibited greater dysfunction of affect circuits whereas ADHD relative to PBD showed greater dysfunction of working memory circuits. In fig 2a, red clusters in the brain picture indicate greater brain activation in the first group compared to the second group of the comparison. Blue clusters indicate less activation in the first group compared to the second group. (DLPFC= dorsolateral prefrontal cortex; IFG=inferior frontal gyrus, VLPFC= ventrolateral prefrontal cortex; ACC=anterior cingulate cortex).

The researchers found that while both disorders show dysfunction in the prefrontal cortex relative to healthy controls, the ADHD group had the most severe dysfunction in this important region. The prefrontal cortex controls behavior, such as impulsivity, and executive function, as well as complex cognitive processes such as working memory, attention, and language.

From a treatment, learning and intervention perspective, the next step for researchers and clinicians is to figure out how to help patients use their prefrontal cortex, Passarotti said.

The researchers also found that while the ADHD group had greater dysfunction in working memory circuits in the brain, the bipolar group had more deficits in regions of the brain involved in emotion-processing and regulation.

Now that researchers are starting to differentiate between the two disorders at a brain network level, rather than just at a behavioral level, the long-term goal is to develop diagnostic tests based on neurological and behavioral markers of illness that can be used in a clinical setting. Currently patients are diagnosed using clinical measures, questionnaires, behavior scales and interviews with parents.

It is difficult for physicians to differentiate between the two disorders behaviorally, which may lead to an incorrect diagnosis and wrong medications, a worsening of symptoms, and greater frustration for children and parents, said Passarotti, a researcher in UIC’s Institute for Juvenile Research.

She said that while researchers still do not understand all of the neurological deficits that characterize ADHD and PBD profiles, they know that drug treatment that works for ADHD does not work for bipolar disorder.

“In fact, if you give a stimulant to a child with bipolar disorder, they become more manic, and this makes their illness even worse, whereas if you give the mood-regulation medicine commonly prescribed for PBD to a child with ADHD, they still show a lot of attention deficits and do not show any improvement,” Passarotti said.

“Our hope is that by better differentiating between these two severe developmental illnesses, we can help develop more accurate diagnoses and more targeted treatments for PBD and ADHD.”

Material adapted from University of Illinois at Chicago.

The public debate on violent crime usually assumes that violence in the mentally ill is a direct result of the perpetrator’s illness. Previous research has also suggested that patients with bipolar disorder – also known as manic-depressive disorder – are more likely to behave violently. However, it has been unclear if the violence is due to the bipolar disorder per se, or caused by other aspects of the individual’s personality or lifestyle.

The new study, carried out by researchers at Karolinska Institutet and Oxford University, is presented in the scientific journal Archives of General Psychiatry. Researchers compared the rate of violent crime in over 3,700 patients with bipolar disorder cared for in Swedish hospitals between 1973 and 2004 with that of 37,000 control individuals from the general public.

21% of patients with bipolar disorder and a concurrent diagnosis of severe substance abuse (alcohol or illegal drugs) were convicted of violent crimes, compared to 5% of those with bipolar disorder but without substance abuse, and 3% among general public control individuals. The differences remained when accounting for age, gender, immigrant background, socioeconomic status, and whether the most recent presentation of the bipolar disorder was manic or depressed.

“Interestingly, this concurs with our group’s previous findings in schizophrenia, another serious psychiatric disorder, which found that individuals with schizophrenia are not more violent than members of the general public, provided there is no substance abuse,” says professor Niklas Långström, head of the Centre for Violence Prevention at Karolinska Institutet, and one of the researchers behind the study.

According to the researchers, the findings support the need for initiatives to prevent, identify and treat substance abuse when fighting violent crime. Additionally, Långström hopes that the results will help challenge overly simplistic explanations of the causes of violent crime.

“Unwarranted fear and stigmatization of mental illness increases the alienation of people with psychiatric disorder and makes them less inclined to seek the care they need”, Långström comments.

Material adapted from Karolinska Institutet.

Reference
Seena Fazel, Paul Lichtenstein, Martin Grann, Guy M Goodwin & Niklas Långström. “Bipolar disorder and violent crime: new evidence from population-based longitudinal studies and systematic review,” Archives of General Psychiatry, online 6 September 2010.

D’Mello presented his findings – which could lead to improved treatments – last week at the American Psychiatric Association’s 2010 annual meeting in New Orleans.

While the connection between such disorders and cardio-metabolic conditions such as heart disease and diabetes has been established, D’Mello also discovered bipolar patients with high blood pressure suffered higher levels of mania.

“There is a large clinical relevance to the finding hypertension could be linked to the severity of bipolar disorders,” he said. “There is some similarity to the pathology of the two conditions; they both can be triggered by stress and are tied to the excretion of norepinephrine, a hormone affecting how the brain reacts to stress.”

Understanding how bipolar disorder and cardio-metabolic conditions are linked could help physicians create more effective treatment options, he added.

“These findings show that we should look to treat hypertension more aggressively in bipolar patients,” said D’Mello, who has been studying the link between psychiatric and medical conditions for decades. “There also is some evidence hypertension may lead to brain lesions; diagnosing high blood pressure and treating it earlier may change the medical outcomes for people battling bipolar disorders.”

In addition, similar to how certain drugs such as lithium do not work as well in bipolar patients who are obese, different medications may be identified that work better.

D’Mello, a professor in MSU’s Department of Psychiatry, part of the colleges of Human Medicine and Osteopathic Medicine, said the next step is to discover how hypertension and other cardio-metabolic disorders interact over the long term.

“Is this just a point of time comparison or an enduring concern? We need to follow people and look at mania ratings over a period of time and not just during a hospital stay,” he said.

Material adapted from Michigan State University by CFisher.

This study is based on previous work led by Mark Zimmerman, MD, director of outpatient psychiatry at Rhode Island Hospital. The previous research involved 700 psychiatric outpatients who were interviewed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID) along with a self-administered questionnaire. The questionnaire asked whether the patient had been previously diagnosed with bipolar or manic-depressive disorder by a health care professional. Of the 700 patients, 145 of those had been previously diagnosed, yet fewer than half of those (43 percent) received a confirmed diagnosis using the SCID. The 82 patients who did not receive a confirmed diagnosis were then classified as the over-diagnosed patients.

In this study, the researchers examined whether a secondary gain such as receiving disability payments might be partially responsible for the over-diagnosis. The 82 over-diagnosed patients from the previous survey were compared to 528 patients who were not diagnosed with bipolar disorder. These patients were interviewed by a diagnostic rater who administered a modified version of the SCID to inquire whether patients had received long-term disability payments because of psychiatric illness in the past five years, and for what length of time they received payments.

Zimmerman says, “We recognize that bipolar disorder is sometimes a severe, chronic illness that interferes with an individual’s ability to maintain gainful employment. Yet when we compared patients who had never been diagnosed with bipolar disorder to the group that we consider over-diagnosed, the over-diagnosed group was significantly more likely to have received disability payments, and for a significantly longer period of time.”

Zimmerman, who is also an associate professor of psychiatry and human behavior at The Warren Alpert Medical School of Brown University, explains the possible reasons for the association between receiving disability payments and the over-diagnosis of bipolar disorder. The patients may have over-reported symptoms to meet the criteria for a bipolar disorder diagnosis if they thought it would qualify them for disability payments, but this is unlikely because they did not do so in the SCID interview. “We believe it is more likely that clinicians sometimes over-diagnose bipolar disorder in complex, chronically ill patients with long histories of depression with co-morbidities that share features of bipolar disorder.” These types of patients are also more likely to be disabled by their psychiatric illness.

The researchers also note that attempts to engage some patients in discussions about alternative diagnostic possibilities or psychotherapeutic interventions instead of pharmacotherapy are sometimes met with resistance. “Not only have we observed bipolar disorder over-diagnosis in our practice, but we have been impressed with some patients’ investment in this diagnosis. We propose that this diagnostic label may be embraced because of the secondary gain accrued from receiving disability payments.”

The findings are limited in that it was conducted in a single outpatient practice, but the researchers believe they are significant enough to be studied in a larger group.

Material adapted from Lifespan by CFisher.

A new diagnostic category for troubled children called Temper Dysregulation Disorder with Dysphoria (TDD), which would to a considerable extent replace the diagnosis of bipolar disorder in children, is one of the most talked-about features of recently released draft revisions to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM). The new diagnosis would focus on negative mood and temper outbursts as their own symptoms, rather than as indications of mania or other elevated mood symptoms associated with bipolar disorder.

The proposal of a new category suggests that the dramatic increase in the number of children diagnosed with bipolar disorder is not appropriate. But “will the TDD diagnosis promote the ultimate goal of psychiatric classification: helping troubled children to flourish?” ask Erik Parens, senior research scholar at The Hastings Center; Josephine Johnston, research scholar at The Hastings Center; and Gabrielle A. Carlson, Director of Child and Adolescent Psychiatry at Stony Brook University School of Medicine. The answer is no, “unless we get serious about reforming pediatric mental health care,” the authors write in an essay, “Pediatric Mental Health Care Dysfunction Disorder?”

“No existing DSM diagnosis conveys the appropriate severity and complexity of these children’s moods and behaviors; the ‘bipolar disorder’ label was meant to provide a home for children who were diagnostically homeless,” according to the authors. “The dispute has been about whether bipolar disorder is the right diagnostic home.”

The TDD label more accurately describes the behavior of most children currently diagnosed as having bipolar disorder, the authors write, and it reflects what is not known, including the outcome of their condition. They add that the new label will assist researchers studying the etiology, treatment, and outcomes of a serious behavioral and mood disturbance.

“But switching from the bipolar label to the TDD label will not decrease the rate of psychopharmacologic treatment,” the authors warn. “If applied trivially to any kind of temper tantrum, it will actually increase medication use.” Children labeled TDD will probably receive many of the same medications currently prescribed for children labeled bipolar disorder, which are associated with significant side effects.

One thing is widely agreed, according to the commentary: treatment with medications alone is seldom sufficient. Yet a recent study of large private insurance databases found that most children prescribed antipsychotic medications did not receive psychosocial treatment, as well. “Troubled children, regardless of their diagnostic label, deserve better,” the authors conclude.

Material adapted from The Hastings Center by CFisher.

Episodic vs. Chronic Irritability
Like BD in adults, some children have classic episodes of mania, with a distinct change in mood ­­ becoming more irritable or euphoric than usual – along with a simultaneous change in sleep, activity, and thought patterns. Instead of such clear-cut episodes interspersed with periods of normal mood or depression, many more children present with chronic, severe irritability. Whether these children also have pediatric BD has been at issue.

To capture these severely irritable children without clear episodes, Leibenluft and her colleagues have defined a syndrome they call severe mood dysregulation (SMD). Youth with SMD share certain overlapping features with their bipolar peers, such as poor frustration tolerance and impaired ability to recognize emotional facial expressions, but differ in symptoms, course, and pedigree.

Leibenluft’s team showed in earlier studies that children with BD tend to come from families with histories of the disorder and tend to carry the disorder into adulthood, while children with SMD don’t. Children with SMD are more prone to developing depression or anxiety disorders rather than BD as adults.

SMD is now embodied in the Temper Dysregulation Disorder with Dysphoria (TDD) category of the recently proposed psychiatric diagnostic manual revision (DSM-V), which cites the NIMH team’s studies in defining TDD. SMD/TDD is much more common than pediatric BD, affecting about 3.2 percent of children, but no less disabling.

Children with BD or SMD both tend to have attention deficit hyperactivity disorder (ADHD) symptoms, but children with just ADHD differ from those with SMD in not experiencing marked irritability, and from those with BD in not having episodes of mania or depression. To further clarify distinctions among these diagnoses, the NIMH researchers are using brain imaging to compare the workings of neural circuits in pediatric BD and these seemingly related disorders.

“We’re finding that the same clinical symptom, or behavioral deficit, may be mediated by more than one brain mechanism,” explained Leibenluft.

Reading Fear into Neutral Faces
Previous studies also suggested that children with BD have weakened connections between the amygdala, the brain’s fear hub, and other brain structures involved in processing facial emotion. These weakened connections may contribute to the children’s impaired ability to recognize emotional expressions.

Amygdala (yellow area where lines intersect) over-activated in subjects with ADHD and under-activated in those with SMD while they rated the fearfulness of neutral faces. (Source: NIMH Section on Bipolar Spectrum Disorders)

In a follow-up study, reported in the January 2010 issue of the American Journal of Psychiatry, Melissa Brotman, Ph.D., Leibenluft and colleagues compared amygdala activity in children with ADHD, BD, SMD, and healthy controls while they rated emotion in neutral faces. Functional magnetic resonance imaging (fMRI) revealed that this task seemed to engage unique neural mechanisms in each syndrome.

For example, when rating how fearful the neutral faces appeared, the amygdala over-activated in ADHD, under-activated in SMD, and ­­ unexpectedly – activated normally in bipolar disorder relative to controls.

In previous such studies, children with bipolar disorder showed increased amygdala activity – and even in this study, they subjectively rated the neutral faces as more fearful than did controls. So the latter outcome may be a fluke. Still, the findings add to evidence of divergence between bipolar and SMD in the way the brain processes facial emotion.

Since studies have shown that depressed children have reduced amygdala activity, and SMD is a risk factor for adult depression, the researchers suggest that amygdala dysfunction in SMD might be a predictor of later depression.

This first fMRI study to include children with SMD and the first to compare amygdala activation across these groups suggests that, despite some overlapping symptoms, the brain may be working differently in each disorder.

Slow to Recognize Emotion
In an earlier study, children with BD, SMD and controls were asked to label the emotion emerging as faces morphed from a neutral to full expression. Children with either BD or SMD took significantly longer than controls before recognizing fear, surprise, disgust and happy expressions, report Brendan Rich, Ph.D., Leibenluft and colleagues in the Spring, 2008 issue of Development and Psychopathology.

(click to enlarge) Children with both bipolar disorder and SMD were slow to identify emotional facial expressions, such as disgust (above) as they morphed from neutral to full intensity. (Source: NIMH Section on Bipolar Spectrum Disorders)

Since another NIMH study had found that this impairment is not shared by children with ADHD or other childhood disorders, the results suggest that the two disorders may be on a continuum in terms of their underlying biological and psychological causes. Yet, the impaired face labelling was linked to different psychosocial impairments in the two groups – perhaps also hinting at some differences in underlying brain mechanisms, suggest the researchers. It was associated with dysfunctional family relationships among children with SMD, in contrast to deficient social reciprocity skills among youth with BD.

Accentuating the Negative
Although chronic severe irritability is the hallmark symptom of SMD, irritability is also common in youth with BD, both within and between manic and depressive episodes. Children with irritability tend to have difficulty coping with frustration. The NIMH researchers had shown earlier that when frustrated by negative feedback, youth with BD emit brain wave patterns signaling impaired attention.

To pinpoint the underlying neural circuitry, the researchers turned to an imaging technique called magnetoencephalography (MEG), which can detect even fleeting, millisecond events deep in the brain. Rich, Leibenluft and colleagues reported on the first MEG study of childhood BD online December 27, 2009 in the journal Depression and Anxiety. They scanned youth with the disorder and controls while they performed an attention task rigged to frustrate them by leading them to believe – for a time – that they were losing money won earlier (Ultimately, their winnings were restored).

(click to elarge) Leibenluft looks on as research fellow Tyler Ard demonstrates the attention task in MEG scanner. Source: NIMH Section on Bipolar Spectrum Disorders

As expected, youth with BD reported being more upset by the frustration-inducing negative feedback than did the controls. This irritability was associated with over-activation of an emotion-processing circuit centered on a brain area earlier implicated in BD called the anterior cingulate cortex (ACC).

Youth with BD showed greater activation than controls after negative feedback (losing money) in an area of the left ACC. By contrast, controls showed greater activation than bipolar youth after positive feedback (winning money) in an area of the right ACC.

Such over-activation in the left ACC likely reflects exaggerated attention and disproportionate thinking about their performance in response to negative feedback among bipolar youth, suggest the researchers. This would exacerbate irritability and frustration, perhaps distracting them from positive information.

Related studies show that children with either SMD or BD experience increased frustration in such attention tasks relative to controls, but the SMD and BD children differ in the way their brains process the tasks. The SMD children’s brains respond more like those of children with ADHD.

Left: Left anterior cingulate cortex (where lines intersect) over-activated in pediatric BD in response to negative feedback. Right: Right anterior cingulate cortex (where lines intersect) under-activated in pediatric BD in response to positive feedback. MEG data superimposed on MRI data. Source: NIMH Section on Bipolar Spectrum Disorders

Different Circuitry May Call for Different Treatments
On the mistaken assumption that they have BD, many children with SMD have been prescribed anticonvulsant and antipsychotic medications. Such misdiagnosis can expose children unnecessarily to risks of serious long-term side effects with these agents, including weight gain, diabetes and heart disease.

Leibenluft’s team is conducting a clinical trial to test whether children with SMD might be better helped instead with treatments more appropriate for depression and anxiety – disorders more related to their illness – and their ADHD symptoms. After discontinuing their other medications, children in the study are first given a stimulant medication, followed by a randomized course of treatment with either an antidepressant or placebo.

“In many ways, this is the single most important study we’re doing, in terms of public health impact,” noted Leibenluft.

Material adapted from NIMH by CFisher.

References
Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Brotman MA, Rich BA, Guyer AE, Lunsford JR, Horsey SE, Reising MM, Thomas LA, Fromm SJ, Towbin K, Pine DS, Leibenluft E. Am J Psychiatry. 2010 Jan;167(1):61-9. Epub 2009 Nov 16.PMID: 19917597

Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation. Rich BA, Grimley ME, Schmajuk M, Blair KS, Blair RJ, Leibenluft E. Dev Psychopathol. 2008 Spring;20(2):529-46.PMID: 18423093

A preliminary study of the neural mechanisms of frustration in pediatric bipolar disorder using magnetoencephalography. Rich BA, Holroyd T, Carver FW, Onelio LM, Mendoza JK, Cornwell BR, Fox NA, Pine DS, Coppola R, Leibenluft E. Depress Anxiety. 2009 Dec 27. [Epub ahead of print] PMID: 20037920

Temper Dysregulation Disorder with Dysphoria (TDD). Download PDF.

Studying these children permits researchers to assess the risk associated with two sources of genetic predisposition to mental disorders. “Such risks will be of use to genetic counselors to inform personal decisions with regard to marriage, family formation, adoption and health insurance planning,” the authors write.

Irving I. Gottesman, Ph.D., Hon.F.R.C.Psych., of the University of Minnesota Medical School, Minneapolis, and colleagues studied a population-based cohort of 2.7 million individuals born in Denmark. The researchers matched records in a general registry of the population with a database of psychiatric admissions. They identified individuals whose parents had both been admitted to psychiatric facilities for schizophrenia and bipolar disorder, and compared the rate of psychiatric admissions for these individuals to those of offspring with one or no parents admitted to psychiatric facilities.

Rates of schizophrenia were highest among offspring of two parents with schizophrenia. Of the 196 couples who both had schizophrenia, 27.3 percent of their 270 children were admitted to a psychiatric facility, increasing to 39.2 percent when schizophrenia-related disorders were included. This compared with a rate of 7 percent among 13,878 offspring of 8,006 couples in which one parent had schizophrenia and 0.86 percent in 2.2 million offspring of 1 million couples in which neither parent was admitted for schizophrenia.

Similarly, the risk of bipolar disorder was 24.9 percent in 146 offspring of 83 parent couples who were both admitted for bipolar disorder (increasing to 36 percent when unipolar depressive disorder was also included). This compared to a risk of 4.4 percent among 23,152 offspring of 11,995 couples with only one parent ever admitted for bipolar disorder and 0.48 percent in 2.2 million children of 1 million couples with neither parent ever admitted.

When one parent had bipolar disorder and the other had schizophrenia, offspring had a 15.6 percent risk of schizophrenia and an 11.7 percent risk of bipolar disorder.

The risks in this population “are of such a magnitude that they command clinical and national public health attention in countries with health care roughly similar to Denmark’s,” the authors write.

“It is important to keep in mind that the yields from genetic epidemiology and the strategies implemented are applicable to groups of people, not to the individuals themselves,” they conclude. “However, by joining advances in molecular genetics that are adapted for use in epidemiological genetic screening, our kinds of data with the risk groups described might lead to a large and rapid step forward in the understanding of the etiologies of major mental disorders.”

Material adapted from JAMA and Archives Journals by CFisher.

The findings come soon after proposed revisions to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) were opened to public comment.

In a paper published in Child and Adolescent Psychiatry and Mental Health, Erik Parens and Josephine Johnston examine the evolution of the diagnosis of bipolar disorder in children and its dramatic increase since the mid 1990s, after the criteria for diagnosis broadened. They emphasize that there is vigorous debate in pediatric psychiatry about whether symptoms in children accurately reflect the criteria for bipolar disorder, particularly for mania.

The increase in cases has led to concerns about accurately defining psychiatric disorders in children as well as the safety and efficacy of resulting pharmacological treatment.

It is difficult to diagnose psychiatric disorders in children, Parens and Johnston write, and many children receiving bipolar diagnoses exhibit behaviors that do not closely fit the disease’s criteria. “Using new labels such as SMD or TDD reflects that physicians do not yet know exactly what is wrong with these children or how to treat it,” said Johnston. “Facing up to this uncertainty could lead to better treatment recommendations and more accurate long-term prognosis.” A new diagnostic category would also help reframe the research agenda.

Their findings come from an interdisciplinary series of workshops funded by a grant from the National Institute of Mental Health. Participants included psychiatrists, pediatricians, educators, bioethicists, parents, and social scientists. Erik Parens is a senior research scholar and Josephine Johnston a research scholar at The Hastings Center, a bioethics research institution.

Among the workshop conclusions:

• The bipolar label may fit poorly many of the children who have received it over the last decade.
• There is debate about what children’s symptoms represent. For example, what is characterized as mania in children is very different from its features in adults. Mania is a hallmark feature of bipolar disorder, formerly known as manic-depressive disorder.
• The bipolar label, which has a strong genetic component, can distract from addressing the family or social context.
• Physicians must be forthcoming with families about uncertainties and complexities in the diagnosis and treatment of bipolar disorder in children.
• Current training practices and reimbursement policies may leave some psychiatrists and pediatricians unable to deliver the comprehensive care that these children need.

The authors also note that, while experts sometimes disagree about labels, the workshop group universally agreed that “children and families can suffer terribly as a result of serious disturbances in children’s moods and behaviors,” and that these troubled children desperately need help. They also write, “It is a deeply regrettable feature of our current mental health and educational systems that some DSM diagnoses are better than others at getting children and families access to [needed] care and services.”

Material adapted from The Hastings Center by CFisher.

Introduction (Continued)
The results add to mounting evidence that major mental disorders overlap at the molecular level. “People who carry the risk versions may differ in some dimension of brain development that may increase risk for mood disorders later in life,” explained Francis McMahon, M.D., of the NIMH Mood and Anxiety Disorders Program, who led the study. McMahon and an international team of investigators, supported, in part by NIMH, report on the findings of their genome-wide meta-analysis online January 17, 2010 in the journal Nature Genetics.

Background
Major mood disorders affect 20 percent of the population and are among the leading causes of disability worldwide. It’s long been known that bipolar disorder and unipolar depression often run together in the same families, hinting at some shared lineage. Yet, until now, no common genes or chromosomal locations had been identified.

McMahon and colleagues analyzed data from five different genome-wide association studies (GWAS) totaling more than 13,600 people, and confirmed their results in 3 additional independent samples totaling 4,677 people.

Findings of This Study
Genetic variations on Chromosome 3 were significantly associated with both mood disorders. The suspect gene, called PBRM1, codes for a protein critical for chromatin remodeling, a key process in regulating gene expression. A neighboring gene is involved in the proliferation of brain stem cells.

Protein produced by PBRM1 gene; Source: UCSC Genome Browser

The researchers pinpointed a “protective” version of the PBRM1 gene that is carried by 41 percent of healthy controls, but only 38 percent of people with bipolar and unipolar depression. The risk version was found in 62 percent of mood disorder cases and 59 percent of controls. The researchers also showed that PBRM1 is expressed more in the prefrontal cortex of people with bipolar disorder than in controls.

Significance
Since mood disorders likely involve altered gene expression during brain development and in response to stress, PBRM1′s profile makes it a good potential candidate gene. This first genetic evidence of unipolar/bipolar overlap is also the first significant genome-wide association with any psychiatric illness in the Chromosome 3p region.

However, the findings underscore limitations of the GWAS approach, which looks for connections to gene versions that are common in the population. Having one copy of this risk variant increases vulnerability for developing a mood disorder by a modest 15 percent. Why do some people with this variant — and presumably other, yet to be discovered, shared risk genes — develop bipolar disorder while others develop unipolar depression or remain healthy? Environmental influences and epigenetic factors may be involved, suggest the researchers, who note that “genetic association findings so far seem to account for little of the inherited risk for mood disorders.”

Bipolar disorder and unipolar depression often run in the same families, as this pedigree diagram illustrates. The new study is the first to trace both illnesses to a shared chromosomal hotspot. Source: NIMH Genetics Initiative Bipolar Disorder Consortium

“Our results support the growing view that there aren’t common genes with large effects that confer increased risk for mood disorders,” said McMahon. “If there were, in this largest sample to date, we would have found them. The disorders likely involve many genes with small effects — and different genes in different families — complicating the search. Rarer genes with large effects may also exist.”

What’s Next?
Ultimately, findings such as these may lead to identification of common biological pathways that may play a role in both unipolar and bipolar illness and suggest strategies for better treatment, said McMahon. The results add to other evidence of overlap that is spurring a new NIMH initiative to make sense of research findings that don’t fit neatly into current diagnostic categories. See: Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research.

Material adapted from National Institutes of Health by CFisher.

Reference
Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.the Bipolar Disorder Genome Study (BiGS) Consortium, McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD, Steele CJ, Breuer R, Strohmaier J, Wendland JR, Mattheisen M, Mühleisen TW, Maier W, Nöthen MM, Cichon S, Farmer A, Vincent JB, Holsboer F, Preisig M, Rietschel M. Nat Genet. 2010 Jan 17. [Epub ahead of print]PMID: 20081856

Bipolar Disorder in Children and Teens: A Parent’s Guide provides a straightforward discussion of the important biopsychosocial foundations and symptoms of this disorder. Other important topics are covered, including frequent co-morbid conditions (e.g., ADHD and anxiety disorders), where to go for help, and crisis management. The e-book also describes the various pharmacotherapies with easy to read summaries of appropriate drugs and their side effects, as well as a brief overview of commonly recommended supportive psychological treatments.

As an additional resource, psychologists who work with patients with Bipolar Disorder may want to read “Cognitive-Behavioral Therapy for Bipolar Disorder, Second Edition” to better understand the nature of this disorder and the currently available researched-based CBT approaches.

Download “Bipolar Disorder in Children and Teens: A Parent’s Guide” here.

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