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A new mouse model of mania
March 12, 2008Bipolar Disorder (BPD or manic-depressive illness) is one of the most serious of all mental disorders, affecting millions of individuals worldwide. Affected individuals alternate between states of deep depression and mania. While depression is characterized by persistent and long-term sadness or despair, mania is a mental state characterized by great excitement, flight of ideas, a decreased need for sleep, and, sometimes, uncontrollable behavior, hallucinations, or delusions. BPD likely arises from the complex interaction of multiple genes and environmental factors. Unlike some brain diseases, no single gene has been implicated in BPD.
A major limitation to progress in research and treatment has been the lack of an appropriate animal model for BPD. This work was developed to create such a model based on a genetically engineered defect in the GluR6 gene. The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with BPD. Kainate receptors respond to the neurotransmitter glutamate, and recent research in mood disorders suggests that the glutamatergic system may play a role in causing mood disorders.
Until now, the role of GluR6 in regulating the mood swings of BPD has been unknown. Furthermore, the gene encoding the GluR6 receptor has recently been linked to treatment emergent suicidal ideation with antidepressants in a pharmacogenetic study. Notably, individuals with bipolar disorder are most susceptible to antidepressant-induced dysphoric states. In this study, mice of several strains were used to investigate this issue. Mice who were missing the GluR6 gene were compared with control mice. The mice underwent a series of tests designed to approximate the symptoms of mania. The researchers found that mice that were missing the GluR6 gene exhibited many of these symptoms. They were more active in multiple tests and super-responsive to amphetamine, which is used in animal models to approximate hyperactivity. These mice also exhibited less anxious or more risk-taking type behavior and less despair-type behavior. They also tended to be more aggressive.
Notably, BPD is most often treated with a class of medications known as mood stabilizers; lithium is perhaps the best known of these medications. The researchers found that chronic treatment with lithium reduced hyperactivity, aggressive displays, and some risk-taking type behavior in mice missing the GluR6 gene. When biochemical tests were conducted, they also suggested that GluR6 may play a unique role in regulating some of the symptoms of mania. This new animal of mania permits researchers to better understand bipolar disorder and to screen for new treatments that if successful in the animal model can then be translated to the clinic.
Molecular Psychiatry
Notably, BPD is most often treated with a class of medications known as mood stabilizers; lithium is perhaps the best known of these medications. The researchers found that chronic treatment with lithium reduced hyperactivity, aggressive displays, and some risk-taking type behavior in mice missing the GluR6 gene. When biochemical tests were conducted, they also suggested that GluR6 may play a unique role in regulating some of the symptoms of mania. This new animal of mania permits researchers to better understand bipolar disorder and to screen for new treatments that if successful in the animal model can then be translated to the clinic.
Molecular Psychiatry
Bipolar Disorder News and Current Bipolar Disorder Events RSSNew study finds that add-on therapy improves depressive symptoms in bipolar disorder
Lingering depression is a serious and common problem in bipolar disorder, and does not resolve well with existing treatments.
Risks and benefits of antipsychotics in children and adolescents
Many of the psychiatric disorders observed in adults have their onset in childhood or adolescence. In fact some studies show that at least 20% of children and adolescents will fulfil a diagnostic criterion for a mental disorder before reaching adulthood.
Children of older fathers more likely to have bipolar disorder
Older age among fathers may be associated with an increased risk for bipolar disorder in their offspring, according to a report in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Family therapy helps relieve depression symptoms in bipolar teens
Family-focused therapy, when combined with medication, appears effective in stabilizing symptoms of depression among teens with bipolar disorder, according to a report in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Sex differences seen in response to common antidepressant
Women with depression may be much more likely than men to get relief from a commonly used, inexpensive antidepressant drug, a new national study finds. But many members of both sexes may find that it helps ease their depression symptoms.
Antidepressants in suicide prevention
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Largest study of its kind implicates gene abnormalities in bipolar disorder
The largest genetic analysis of its kind to date for bipolar disorder has implicated machinery involved in the balance of sodium and calcium in brain cells.
Psychiatrists shift away from providing psychotherapy
A declining number of office-based psychiatrists appear to be providing psychotherapy to their patients, according to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
The ECNP consensus statement on bipolar depression
Bipolar disorder is one of the most complex and challenging mental disorder in the spectrum. Bipolar disorder is typically associated with considerable acute and longterm treatment needs and may be associated in the course of illness with times of tremendous social burden for both the individual and family.
Poor sleep linked to suicidal behavior among children and adolescents with depressive episodes
A research abstract that will be presented on Thursday at SLEEP 2008, the 22nd Annual Meeting of the Associated Professional Sleep Societies (APSS), finds a link between poor sleep and suicidal behavior among children and adolescents with depressive episodes.
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