Category: Bipolar Disorder

Common genetic variants contribute to the risk of schizophrenia and bipolar disorder, an international research consortium has discovered.

Schizophrenia and bipolar disorder are common and often devastating brain disorders, affecting around one per cent of the world's population. A team including Cardiff University scientists has found new molecular evidence that 11 genetic regions have strong links with these diseases, including six regions not previously observed. The researchers also found that many of these DNA variations contribute to both diseases.

The findings, reported by the Psychiatric Genome-Wide Association Study Consortium (PGC), represent significant advances in these severe and debilitating disorders.

The findings, based on genetic data from tens of thousands of patients, have just been published online in two papers in the journal Nature Genetics. Professors Michael O'Donovan, Michael Owen and Nick Craddock from the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff's School of Medicine, Cardiff University, made a significant contribution of data, analysis and management to the study.

Professor O'Donovan said: "The genetic variants we have identified are common in the population — everyone carries many of them, but people with the disorders carry more.

"The success of this study demonstrates the need for international co-ordination in harnessing data from very large samples to exploit the power of genetics to reveal new insights. Over the next two years we expect to have data from study samples that are three or four times larger than those we have now, and this can be expected to have the same impact for our research as ever more powerful particle accelerators have had in physics."

Professor Owen added: "Many genes are clearly involved in these disorders and it will be a few years yet till we are able to see a large part of the picture. However, for the first time, we are in a position to make tentative functional links between some of the genes identified.

"One particularly exciting finding is the involvement of a type of molecule, known as a microRNA, which acts as a molecular switch to turn off other genes. This microRNA is also known to regulate aspects of the development and maturation of nerve cells in the brain. The findings suggest disruption of these development processes as likely factors in the origins of mental disorder."

Both schizophrenia and bipolar disorder usually strike in late adolescence or early adulthood. Some of the most prominent symptoms in schizophrenia are persistent delusions, hallucinations and cognitive problems. Bipolar disorder (or manic-depressive illness) is characterized by episodes of severe mood problems including mania and depression. Despite the availability of treatments, these illnesses are usually chronic, often leads to prolonged disability and personal suffering. Family history is a strong risk factor for both disorders. The new findings are further evidence for the general assumption that dozens of genes, along with environmental factors, contribute to disease risk.

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Journal References:

1. Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 2011; DOI: 10.1038/ng.940
2. Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics, 2011; DOI: 10.1038/ng.943

Recognition of bipolar disorder in adolescents is now clearly established. However, whether bipolarity exists in children remains controversial despite numerous studies that have been conducted on this topic in the last fifteen years. Since the diagnosis of bipolar disorder in children has been rising for the past ten years, clinicians, researchers, parents, and others who care for children are left wondering what accounts for this dramatic increase in diagnosing pediatric bipolar disorder (Dickstein, 2010): is it better recognition of an important psychiatric disorder or is it due to overdiagnosis, misdiagnosis, or a diagnostic trend? In response to this increase, both clinical and research interest in pediatric bipolar disorders have surged, including a re-examination of the diagnostic criteria for this condition based on developmental and neurobiological findings.

Bipolar disorder is a clinically severe affective disorder, in which mood typically swings from the manic pole of euphoria and/or extreme irritability to depression and loss of interest or pleasure. Mixed illness episodes are characterized by both manic and depressive symptoms.

Bipolar disorder can be divided into two major subtypes — bipolar type I and bipolar type II -, although further extension of the bipolar spectrum may be of clinical relevance.

• Bipolar type I disorder is characterized by a history of at least one manic episode, with or without depressive symptoms.
• Bipolar type II disorder is characterized by the presence of both depressive symptoms and a less severe form of mania (´hypomania´).

The periods between acute illness episodes may last months or even years early in the course of the disease, but later these symptom-free periods tend to decrease. ´Rapid cycling´ is a specific course variant which is defined by the occurrence of 4 or more episodes per year.

Bipolar disorder in children and adolescents

Affecting 3-5% of the general population, bipolar disorder is a significant health problem due to its early onset and its chronic, life-long, and relapsing course associated with great impairment. In children and adolescents the illness results in considerable functional limitations and high rates of psychiatric hospitalization (Axelson et al., 2006). According to retrospective studies, 20-60% of adults with bipolar disorder had their first symptoms before the age of 20 years (Lish et al., 1994; Perlis et al., 2004).

Diagnosis

To diagnose bipolar I disorder in adolescents, adult criteria (DSM-IV) are used except that (NICE Guidelines, 2006):

• Mania must be present.
• Euphoria must be present most of the time (in the course of the past 7 days).
• Irritability has to be noted if it is episodic, severe, results in impaired function and is not in character or is out of keeping with the context.

The specific phenomenology of bipolar disorder in adolescents is characterized by (Birmaher et al., 2006; Carlson et al., 1994):

• More mixed episodes than pure manic ones
• Frequent irritability and aggressive behaviour
• Psychotic features in 30-50% of the acute episodes (which may lead to diagnosis errors in 50% of the cases)
• More often observed rapid cycling profile
• Sexual disinhibition,
• High rates of comorbidities such as Attention Deficit Hyperactivity Disorder (ADHD), substance abuse, conduct and anxiety disorders

Clinical features such as euphoria, grandiosity, hypersexuality, racing thoughts, and decreased need for sleep are typical for mania associated with primary bipolar disorder in order to distinguish it from patients with primary ADHD (Birmaher et al., 2006).

The younger the child, the rarer is the condition of bipolar disorder. However, there is no disputing that a substantial number of pre-adolescents have symptoms of mania, usually superimposed on a number of diverse developmental and psychiatric conditions (Carlson, 2005). Recent studies have shown that 'manic symptoms' in children may be more common than once thought. The need to avoid confusing terminology with bipolar disorder is now consensual (Dickstein, 2010). Whether chronic manic symptoms in children represent (1) a developmental disorder that will change during adulthood; (2) an early onset bipolar I disorder; (3) a new subtype of bipolar disorder (e.g. chronic with rapid cycling); or (4) a developmental risk of later bipolar I disorder (narrow phenotype) still needs further research (Carlson, 2005).

A developmental view is crucial to understanding the complex of manic symptoms in children and adolescents.

Is there a continuum between pediatric bipolar disorder and bipolar type I disorder in adolescents?

There are very few arguments to support the hypothesis that bipolar disorder in adolescents (clearly defined illness episodes and so-called euthymic periods without any symptoms) and so-called 'paediatric bipolar disorder' are the same disorder or two disorders related in a common continuum. Furthermore, youths with bipolar disorder and comorbid ADHD tend to be less responsive to drugs used in bipolar disorder, suggesting that chronic manic symptoms comorbid with ADHD in youth may not be the same condition or a continuum rather than typical cycloid bipolar disorder (Consoli et al., 2007).

A novel approach suggests a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype (Leibenluft et al., 2003). The narrow phenotype of mania includes mostly adolescents with clear-cut episodes of euphoric mania. On the other hand, the broad phenotype called ´Severe Mood Dysregulation´ is exhibited by younger patients who have a chronic, non-episodic course of illness that does not include the hallmark symptoms of mania, but shares with the narrower phenotypes the symptoms of severe irritability and ADHD-like hyperarousal. Indeed, these patients appear to better respond to pharmacological and non-pharmacological ADHD-like treatments (Waxmonsky et al., 2008).

This approach and subsequent research have given rise to the new diagnosis of Temper Dysregulation Disorder with Dysphoria (TDDD), which means a potential change in the diagnostic classification system DSM-V scheduled for publication in May 2013. However, a diagnosis of TDDD excludes the ADHD-like symptom of hyperarousal due to concerns that it would potentially lead to an increase in the diagnosis of ADHD. In general, such criteria have sparked an incredibly productive line of research demonstrating phenomenological differences (episodic vs. chronic course, euphoric vs. irritable mood) and initiating discussions that are relevant to clinicians and researchers alike (Dickstein, 2010; Leibenluft, 2011; Masi et al., 2008).

Treatment of bipolar disorder in youth

Pharmacological therapy

Appropriate treatment for children and adolescents with bipolar disorder has essential benefit with regard to school performance, academic or occupational impairment, relationship stress, comorbid substance use, and prevention of suicides. Pharmacotherapy of mania comprises so-called mood stabilizers (e.g. lithium), atypical or second-generation antipsychotics (SGAs) and typical antipsychotics (chlorpromazine). The use of mood stabilizers or antipsychotics in the treatment of children and adolescents appears to be of limited value when a comorbid condition such as ADHD occurs, unless aggressive behavior is the target symptom (Consoli et al., 2007).

Adverse subjective effects play a central role in the experience of taking antipsychotic drugs (Moncrieff et al., 2009). In adults, second-generation antipsychotics (SGAs) have shown a good benefice/risk ratio in bipolar disorder with a low frequency of extrapyramidal motor syndrome (EPS) and a moderate frequency of metabolic adverse effects such as metabolic syndrome and diabetes. Yet limited knowledge is available on the use of SGAs in children and adolescents. To assess the benefice/risk ratio of SGAs in children and adolescents, a Bayesian meta-analysis with a total of 4015 patients recently analyzed 41 short-term (3-12 weeks) controlled studies that evaluated SGAs adverse effects in youths, including 12 in youths with bipolar disorder (Cohen et al., submitted for print).

Compared with adults, youths were found to be more vulnerable to adverse effects of SGAs. All SGAs increased the risk of somnolence/sedation. Furthermore, substance-specific significant treatment-related changes compared with placebo were observed regarding weight gain, metabolic variables (including prolactin) and extrapyramidal-motor symptoms.

Second-generation antipsychotics (SGAs) represent an efficacious treatment for children and adolescents with bipolar disorder, whereby different tolerability profiles should be considered in making treatment decisions (Cohen et al., submitted for print).

Non-pharmacological therapies

Besides pharmacological treatment, educational and psychosocial strategies including psychotherapy, promotion of compliance with treatment, and education of patients and their families, are essential in the treatment of bipolar disorder in youth in order to improve the treatment outcome.

In case of no response to pharmacological treatment, electroconvulsive therapy (ECT) has proven to be a safe and effective treatment for both manic and depressive episodes in adolescents with severe illness (Cohen et al., 1997). Regarding the long-term outcome of adolescents who receive ECT, findings suggest that adolescents given ECT for bipolar disorder do not differ in subsequent school and social functioning from carefully matched controls (Taieb et al., 2002), and adolescents treated with ECT do not suffer measurable cognitive impairment at long-term follow-up (Cohen et al., 2000). In addition, an assessment of patients´ and parents´ experiences and attitudes towards the use of ECT in adolescence indicates that, despite negative views about ECT in public opinion, adolescent recipients and their parents share overall positive attitudes towards ECT (Taieb et al., 2001).

Future perspectives

In the past decade, structural and functional imaging studies via magnetic resonance (MRI, fMRI) have yielded greater understanding of the neurobiology of bipolar disorder in children and adolescents. Since current findings indicate that youths with bipolar disorder have fundamental alterations in the brain/behaviour interactions that underlie emotional processing, future studies could evaluate how medications or psychotherapies can ameliorate these brain/behaviour interactions (Dickstein, 2010). The European College of Neuropsychopharmacology (ECNP) supports networks of clinicians who seek to improve treatment in children with bipolar disorder. Since early intervention may improve diagnosis, treatment studies are an important objective for future research in Europe (Goodwin et al., 2008).

Conclusion

In recent years, a considerable increase in the number of children and adolescents evaluated, diagnosed and treated for bipolar disorder has been noted.

Bipolar-like symptoms are quite frequent in prepubertal children, but the age at which bipolar disorder can first be diagnosed remains controversial. Current neurobiological findings have advanced our understanding of emotional function and dysfunction in youth.

Developmental aspects and environmental factors are crucial regarding the onset and progression of bipolar disorder in children and adolescents. From a developmental view, bipolar disorder in adolescents and so-called 'paediatric bipolar disorder' are not the same disorder or two disorders related in a common continuum.

Differential diagnosis is important to distinguish bipolar disorder from Attention Deficit Hyperactivity Disorder (ADHD) or conduct disorders in children and adolescents.

Treatment of bipolar disorder in youths comprises pharmacological and non-pharmacological strategies. Differences in the tolerability profiles of medications should be considered in making treatment decisions and optimizing the benefice/risk ratio.

In coming years, recognising and diagnosing bipolar disorder in children should be more strongly based on biological markers such as brain structure and neural circuits. Combined with clinical history, this approach is expected to result in improved, more specific and accurate diagnosis and treatment.

References

1. Axelson D, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006;63:1139-1148

2. Birmaher B, Axelson D, Strober M, et al. Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006;63:175-183

3. Carlson GA. Early onset bipolar disorder: clinical and research considerations. J Clin Child Adol Psychology 2005;34:333-343.

4. Carlson GA, Fennig S, Bromet EJ. The confusion between bipolar disorder and schizophrenia in youth: where does it stand in the 1990s? J Am Acad Child Adolesc Psychiatry 1994;33:453-460

5. Charfi F, Cohen D. THDA et trouble bipolaire sont-ils lies? Neuropsychiatrie de l´enfance et de l´adolescence 2005;53:121-127

6. Cohen D. Probabilistic epigenesis: an alternative causal model for conduct disorders in children and adolescents. Neurosci Biobehav Rev 2010;34:119-129

7. Cohen D. Bipolar episodes in adolescents: diagnostic issues and follow-up in adulthood. Encephale 2009;35(Suppl. 6):S224-230

8. Cohen D, Taieb O, Flament M, et al. Absence of cognitive impairment at long-term follow-up in adolescents treated with ECT for severe mood disorder. Am J Psychiatry 2000;157:460-462

9. Cohen D, Paillère-Martinot ML, Basquin M. Use of electroconvulsive therapy in adolescents. Convuls Ther 1997;13:25-31

10. Consoli A, Bouzamondo A, Guilé JM, et al. Comorbidity with ADHD decreases response to pharmacotherapy in children and adolescents with acute mania: evidence from meta-analysis. Can J Psychiatry 2007;52:323-328

11. Consoli A, Deniau E, Huynh C, et al. Treatments in child and adolescent bipolar disorders. Eur Child Adolesc Psychiatry 2007;16:187-198

12. Consoli A, Brunelle J, Bodeau N, et al. Medication use in adolescents treated in a French psychiatric setting for acute manic or mixed episode. J Can Acad Child Adolesc Psychiatry 2009;18:231-238

13. Dickstein D. The diagnostic dilemma: why we need to change how we diagnose bipolar disorder in children. Cerebrum, November 2010;1-13

14. Geller B, Luby J. Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1997;36:1168-1176

15. Goodwin GM, Anderson I, Arango C, et al. ECNP consensus meeting. Bipolar depression. Nice, March 2007. European Neuropsychopharmacology 2008;18:535-549

16. Leibenluft E, Charney DS, Towbin KE, et al. Defining clinical phenotypes of juvenile mania. Am J Psychiatry 2003;160:430-437

17. Leibenluft E. Severe mood dyregulation, irrability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry 2011;168:129-42

18. Lish JD, Dime-Meenan S, Whybrow PC, et al. The National Depressive and Manic-Depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994;31:281-294

19. Masi G, Milone AR, Manfredi A et al. Comorbidity of conduct disorder and bipolar disorder in referred children and adolescents. Journal of Child and Adolescent Psychopharmacology 2008;18:271-279

20. Moncrieff J, Cohen D, Mason JP. The subjective experience of taking antipsychotic medication: a content analysis of Internet data. Acta Psychiatr Scand 2009;120:102-111

21. NICE Clinical Guideline 38. Bipolar disorder. The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. London, 2006

22. Perlis RH, Miyahara S, Marangell LB. Long-Term Implications of Early Onset in Bipolar Disorder: Data from the First 1000 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Biol Psychiatry 2004;55:875-881

23. Taieb O, Flament MF, Corcos M, et al. Electroconvulsive therapy in adolescents with mood disorder: patients´ and parents´ attitudes. Psychiatry Res 2001;104:183-190

24. Taieb O, Flament MF, Chevret S, et al. Clinical relevance of electroconvulsive therapy (ECT) in adolescents with severe mood disorder: evidence from a follow-up study. Eur Psychiatry 2002;17:206-212

25. Waxmonsky J, Pelham WE, Gnagy E et al. The efficacy and tolerability of methylphenidate and behavior modification in children with attention-deficit/hyperactivity disorder and severe mood dysregulation. J Child Adolesc Psychopharmacol 2008;18:573-88

Researchers from the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital have conducted a study which has found striking brain similarities in bipolar disorder and schizophrenia. The research has also pinpointed for the first time that a process which controls how information is transmitted from neuron to neuron in the brain is altered in both conditions and may potentially contribute to the developments of improved treatments in the future.

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.

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Journal Reference:

1. 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

Positive emotions like joy and compassion are good for your mental and physical health, and help foster creativity and friendship. But people with bipolar disorder seem to have too much of a good thing. In a new article to be published in the August issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science, psychologist June Gruber of Yale University considers how positive emotion may become negative in bipolar disorder.

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're 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 aren't 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. 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 were 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 don't 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 don't 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."

 Mood swings are not always best understood as an illness called 'bipolar disorder', and medication is not the only way to cope with them, says a British Psychological Society report. The report, Understanding Bipolar Disorder, which the Society has made available as a free download throughout the month of July, gives new hope to people diagnosed with bipolar disorder (about 1 to 2 percent of the population).

This in-depth review of recent research was authored by Professor Steven Jones of Lancaster University and a team of leading clinical psychologists, working in partnership with service users. It suggests that a tendency to extreme moods can have significant benefits as well as sometimes leading to problems.

Many people who have been reported as having the diagnosis are also extremely creative and successful individuals. Examples include government press advisor Alistair Campbell, actress Carrie Fisher, actor Stephen Fry, comedian Paul Merton, and television presenters Gail Porter and Bill Oddie.

The report also suggests that these mood swings are more extreme forms of the variations we all experience and can result from life events rather than just brain chemistry. It is not always helpful to think of this as an 'illness', and doctors and other health workers may sometimes give unhelpfully negative messages about what the diagnosis means, for example encouraging people to lower their expectations of what they can achieve in life.

The report also suggests that although medication can be helpful for some people, it does not help everyone. Some people prefer instead to think of themselves simply as someone who tends to experience more extreme lows and highs than others, and to manage this by adapting their lifestyle or using psychological therapy.

The report argues that clinical services need to recognise the expertise of service users and work with them towards their own individual goals. One of the authors, Joanne Hemmingfield, said: "As a service user myself I believe that this report provides a message of hope for people with bipolar disorder which is in stark contrast to the messages most people have received in the past."

Clare Dolman, Chair of MDF the Bipolar Organisation, said: "As the national bipolar charity, we welcome this report by some of the UK's most distinguished psychologists, led by Professor Steve Jones of the Spectrum Centre. It is very encouraging that 'Understanding Bipolar Disorder' highlights the potential positive aspects of living with the condition as well as the negative, and paints a more hopeful picture of the path to recovery by combining psychological approaches with medication where necessary.

"The report offers a clear and accessible account of the psychological perspective and we would recommend anyone interested in gaining a more comprehensive understanding of the condition to read it."

Understanding Bipolar Disorder can be downloaded from the BPS Shop: http://www.bpsshop.org.uk/Understanding-Bipolar-Disorder-P1280.aspx. To download it you must register with the site first, but the download is free after you have done so.

Omega 3 fatty acids may be beneficial for more than just the heart. Researchers at the Indiana University School of Medicine have found at a molecular level a potential therapeutic benefit from these dietary supplements for treating alcohol abuse and psychiatric disorders.

In a multi-year study, researchers showed conclusive behavioral and molecular benefits for omega 3 fatty acid given to mice models of bipolar disorder. The fatty acid DHA, which is one of the main active ingredients in fish oil, "normalized their behavior," according to Alexander B. Niculescu, M.D., Ph.D., associate professor of psychiatry and the lead author of the study reported online in the Nature Publishing Group journal Translational Psychiatry.

Using a stress-sensitive mouse model of bipolar disorder developed in his lab, Dr. Niculescu and his colleagues studied the influence of dietary DHA. The mice have characteristic bipolar symptoms including being depressed and, when subjected to stress, becoming manic.

"The mice that were given DHA normalized their behavior, they are not depressed and when subjected to stress, they do not become manic," said Dr. Niculescu. "When we looked into their brains, using comprehensive gene expression studies, we were surprised to see that genes that are known targets of psychiatric medications were modulated and normalized by DHA."

An unexpected finding of the research was the discovery that the mice given DHA also showed a reduced desire for alcohol.

"These bipolar mice, like some bipolar patients, love alcohol. The mice on DHA drank much less; it curtailed their alcohol abusive behavior," he said, adding that this is a completely novel finding. To verify this finding, the researchers studied another well-established animal model of alcoholism, the alcohol preferring P rats, and obtained similar results.

"We believe a diet rich in omega 3 fatty acids may help the treatment and prevention of bipolar disorder, and may help with alcoholism as well," he said.

The researchers also found correlations between mouse brain molecular changes and molecular markers in their blood, so called "biomarkers."

"There is now substantial evidence at the molecular level that omega-3 fatty acids work on the brain in ways similar to psychiatric drugs," said Dr. Niculescu. "With these biomarker findings, we can now move forward as a field and do more targeted clinical studies in humans."

Omega 3 fatty acids are known to be good for one's health, good for one's brain, and lack major side-effects, as opposed to some psychiatric medications, he said. Perhaps, he said, omega 3 fatty acid could in the future be used as an adjuvant treatment to minimize the amount of psychiatric drugs needed to produce the same effect, especially in pregnant women or women who intend to get pregnant.

"A lot more work needs to be done in this area," Dr. Niculescu said.

The research was supported by a National Institutes of Health Director's New Innovator Award grant to Dr. Niculescu.

Other authors are Helen Le-Niculescu Ph.D., Natalie J. Case M.Sc., Leslie Hulvershorn, M.D. , Sagar D. Patel , Dean Bowker, Jyoti Gupta, M.D., Richard Bell, Ph.D., Howard J. Edenberg, Ph.D. , Ming T. Tsuang, M.D., Ph.D. , Ronald Kuczenski, Ph.D., Mark A. Geyer, Ph.D., and Zachary A. Rodd, Ph.D.

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Journal Reference:

1. H Le-Niculescu, Y Balaraman, S D Patel, M Ayalew, J Gupta, R Kuczenski, A Shekhar, N Schork, M A Geyer, A B Niculescu. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms. Translational Psychiatry, 2011; 1 (5): e9 DOI: 10.1038/tp.2011.9

A new study by motor control and psychology researchers at Indiana University suggests that postural control problems may be a core feature of bipolar disorder, not just a random symptom, and can provide insights both into areas of the brain affected by the psychiatric disorder and new potential targets for treatment.

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 of the study "Postural control in bipolar disorder: Increased sway area and decreased dynamical complexity," published last week in the Public Library of Science ONE.

"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."

The study appears in the online journal PLoS ONE.

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.

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Journal Reference:

1. Amanda R. Bolbecker, S. Lee Hong, Jerillyn S. Kent, Mallory J. Klaunig, Brian F. O'Donnell, William P. Hetrick. Postural Control in Bipolar Disorder: Increased Sway Area and Decreased Dynamical Complexity. PLoS ONE, 2011; 6 (5): e19824 DOI: 10.1371/journal.pone.0019824

The future mood swings of people with bipolar disorder can be predicted by their current thoughts and behaviour, a study published April 19, 2011 has found.

Psychologists from the Universities of Manchester and Lancaster say their findings are important because they mean talking therapies, like cognitive behavioural therapy (CBT), could prove effective treatments for the condition.

People with bipolar 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.

A study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide.

Johns Hopkins scientists, reporting in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found more than normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior.

The researchers say the findings could lead to better suicide prevention efforts by providing new directions for research and drug development.

"We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," says study leader Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost three times as likely.

Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder. By using only DNA from people with bipolar disorder, the researchers say they were able to control for mental illness and narrow in on what may cause one group to attempt suicide and another to control those urges.

Suicide is estimated to kill 1.4 percent of the U.S. population, and roughly 4.6 percent of the population has attempted suicide at least once, Willour says. Among people with bipolar disorder, 47 percent think about killing themselves while 25 percent actually try to do it, she says.

Willour says the next steps are to replicate these findings and to determine the exact biological mechanisms through which these genetic risk factors increase the risk for suicidal behavior.

"What's promising are the implications of this work for learning more about the biology of suicide and the medications used to treat patients who may be at risk," Willour says. "Not everyone with bipolar disorder can take lithium because of its side effects. If we could give them another option, that would be fantastic."

The study was funded by grants from the National Institute of Mental Health and the American Foundation for Suicide Prevention.

Other Hopkins researchers who participated in the study are Fayaz Seifuddin, M.S.; Pamela B. Mahon, Ph.D.; Dubravka Jancic, Ph.D.; alex Pirooznia, M.D., Ph.D.; Barbara Schweizer, R.N., B.S.; Fernando S. Goes, M.D.; Francis Mondimore, M.D.; Dean F. MacKinnon, M.D.; J. Raymond DePaulo Jr., M.D.; Peter P. Zandi, Ph.D.; and James B. Potash, M.D., M.P.H.

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Journal Reference:

1. V L Willour, F Seifuddin, P B Mahon, D Jancic, M Pirooznia, J Steele, B Schweizer, F S Goes, F M Mondimore, D F MacKinnon, R H Perlis, P H Lee, J Huang, J R Kelsoe, P D Shilling, M Rietschel, M Nöthen, S Cichon, H Gurling, S Purcell, J W Smoller, N Craddock, J R DePaulo, T G Schulze, F J McMahon, P P Zandi, J B Potash. A genome-wide association study of attempted suicide. Molecular Psychiatry, 2011; DOI: 10.1038/mp.2011.4

A new study provides fascinating insight into the genetic basis of bipolar disorder, a highly heritable mood disorder characterized by recurrent episodes of mania and depression. The research, published online February 24 in the American Journal of Human Genetics, identifies a previously unrecognized susceptibility factor for bipolar disorder.

Genome-wide association studies (GWAS) provide a way to systematically sort through all the DNA of many individuals in order to identify genetic variations associated with a particular disease. However, thus far these studies have not been as successful in bipolar disorder as they have been for several other common diseases, such as type II diabetes, Crohn disease, and schizophrenia. Dr. Sven Cichon, from the University of Bonn in Germany, together with his colleagues Dr. Markus M. Nöthen (University of Bonn) and Dr. Marcella Rietschel (Central Institute of Mental Health, Mannheim), led a GWAS and a critical two-step follow-up study of samples from a great number of clinically well-characterized European, American, and Australian individuals with bipolar disorder.

Dr. Cichon and colleagues found that genetic variation in the gene neurocan (NCAN) showed a significant association with bipolar disorder in thousands of patients. Importantly, in a follow up study, these findings were replicated in tens of thousands of individual samples of bipolar disorder. The researchers went on to show that the mouse version of this gene, which is written Ncan and is thought to be involved in neuronal adhesion and migration, is strongly expressed in brain areas associated with cognition and the regulation of emotions.

Although mice without functional Ncan did not exhibit obvious defects in brain structure or basic cell communication, there did appear to be some perturbation in mechanisms associated with learning and memory, mechanisms that have been associated with the cognitive deficits observed in bipolar disorder. However, the authors caution that Ncan-deficient mice need to be re-examined for more subtle brain changes and behavioral abnormalities.

"Our results provide strong evidence that genetic variation in the gene NCAN is a common risk factor for bipolar disorder," concludes Dr. Cichon. "Further work is needed now to learn more about the biological processes that NCAN is involved in and how NCAN variants disturb neuronal processes in patients with bipolar disorder."

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Journal Reference:

1. Sven Cichon, Thomas W. Mühleisen, Franziska A. Degenhardt, Manuel Mattheisen, Xavier Miró, Jana Strohmaier, Michael Steffens, Christian Meesters, Stefan Herms, Moritz Weingarten et al. Genome-wide Association Study Identifies Genetic Variation in Neurocan as a Susceptibility Factor for Bipolar Disorder. The American Journal of Human Genetics, 2011; DOI: 10.1016/j.ajhg.2011.01.017