Indiana University Neuroscientists Identify Bipolar Disorder Genes, Pathways
Main Category: BipolarAlso Included In: Genetics; Neurology / Neuroscience; Psychology / Psychiatry
Article Date: 24 Nov 2008 - 0:00 PDT
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Neuroscientists at the Indiana University School of Medicine have created the first comprehensive map of genes likely to be involved in bipolar disorder, according to research published online Nov. 21 in the American Journal of Medical Genetics.
The researchers combined data from the latest large-scale international gene hunting studies for bipolar disorder with information from their own studies and have identified the best candidate genes for the illness.
The methodology developed at the IU Institute of Psychiatric Research enabled Alexander B. Niculescu III, M.D., Ph.D., and his team to mine the data from the genome-wide association studies and other study results on the levels of gene activity in human blood samples and in animal models. Genes with the highest levels of prominence were determined to be the most active in contributing to the disorder.
The researchers also were able to analyze how these genes work together and created a comprehensive biological model of bipolar disorder.
"Based on our work, we now project that there will be hundreds of genes - possibly as much as 10 percent of the human genome - involved in this illness," said Dr. Niculescu, who is an assistant professor of psychiatry and director of the laboratory of neurophenomics (http://www.neurophenomics.info/) at the IU School of Medicine. "Not all genetic mutations will occur in every individual with bipolar disorder. Different individuals will have different combinations of genetic mutations. This genetic complexity is most likely what made past attempts to identify genes for the disorder through genetic-only studies so difficult and inconsistent."
Dr. Niculescu compared the process to a Web search. "The process was similar to a Google approach, the more links there are to a page on the Internet, the more likely it is to come up at the top of your search list. The more experimental lines of evidence for a gene, the higher it comes up on your priority list of genes involved in the disorder."
Until now there have been few statistically significant findings in searches of the human genome as it applies to bipolar disorder, he said.
"By integrating the findings of multiple studies, we were able to sort through, identify genes that were most likely to be involved in bipolar disorder, and achieve this major breakthrough in our understanding of the illness," Dr. Niculescu said.
Bipolar disorder, sometimes called manic depression, affects nearly 2.3 million Americans. A serious illness, people who suffer from it can experience mild or dramatic mood swings, shifts in energy and a diminished capacity to function.
Dr. Niculescu, a practicing psychiatrist and a molecular geneticist, said this work opens exciting avenues for psychiatric researchers and clinicians, as well as for patients and their families.
"First and foremost, these studies will lead to a better understanding of bipolar and related disorders," he explained. "Second, the researchers now plan to study individuals to see which combination of genes is present in individuals to come up with a genetic risk score."
The goal, he said, is to be able to apply the risk score to test individuals even before the illness manifests itself for preventive measures - lifestyle changes, counseling, low-dose medications - or to delay or stop the illness from developing.
"Third, in individuals who already have the illness, genetic testing in combination with blood biomarkers for the disease, could help determine which treatments works best so personalized treatments could be developed," Dr. Niculescu said.
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The research was done in collaboration with colleagues at the Scripps Research Institute, the University of California- San Diego, SUNY Upstate medical University and the National Institute of Mental Health. IU researchers involved were Helen Le-Niculescu, Ph.D., John I. Nurnberger, M.D., Ph.D., Meghana Bhat, M.D., and Sagar Patel.
Grant funding for the research was provided by National Institute of Mental Health.
Source: Mary Hardin
Indiana University
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Mental Disorders
posted by Dan on 8 Jan 2009 at 10:54 amBipolar Disorder (manic-depressive illness), if a disorder at all, has been defined as a major affective mood disorder in which one alternates between the mental states of deep and brutal depression and inflated elation- with the depressive episodes occurring more frequently. The disorder affects one’s cognition, emotions, perceptions, and behavior- along with psychosomatic presentations (such as pain with depressive episodes, for example). It is thought to be due to a physiological dysfunctional brain in one affected with bipolar disorder, yet the etiology remains entirely unknown. It is also believed that bipolar disorder presents itself when the affected one is between the ages of 15 and 25 years old. The disorder was entered in the psychiatrists’ bible, the DSM, in 1980. Also, bipolar disorder is thought to be correlated with creativity and accelerated growth of neurons if one is affected by it.
Research has determined that as many as 15 to over 30 percent of bipolar disorder patients commit suicide if they are untreated. Also, as many as half of those affected with bipolar disorder also have at times severe substance abuse issues along with this disorder as well. Bipolar patients are also often experiencing anxiety issues that vary, and are treated often as such. The disorder varies as far as severity goes- with some bipolar disorder patients being more affected than others. In fact, there are at least 6 classifications of bipolar disorder, according to the DSM. Bipolar patients are thought to be symptomatic half of their lives- with depressive episodes occurring more frequently than manic ones. When symptomatic, bipolar patients are thought to be rather disabled, according to some. As many as half of those suspected as having a bipolar disorder are thought to have at least one parent with some sort of mood disorder, which suggests a genetic predisposition to the disorder.
The diagnosis has become more frequent recently. In one decade, the assigned diagnosis of bipolar disorder rose from being about 25 per 100 thousand people to being 1000 per 100,000 people. Most diagnosed with bipolar disorder are not diagnosed based on solid, comprehensive, or psychiatric review that is often absent of valid or standard diagnostic methods. Some believe as many as 5 percent of the human population may be affected by bipolar disorder- which includes as many as 12 million people in the United States. A subjective questionnaire called the Mental Status Examination is often utilized when diagnosing one suspected has having bipolar disorder. Many believe the diagnosis has increased recently due to the progressive treatment options now available. It is an argument of increased awareness versus over-diagnosis.
Yet the diagnosis is vague, as children and adolescents are often absent in research with bipolar disorder. Many younger than 18 years of age are prescribed atypical anti-psychotics as first line treatment, which is largely not recommended as treatment options. In fact, close to half a million of those younger than 18 years of age are prescribed the atypical anti-psychotic Risperdal alone, it has been determined. The class of medications overall is thought to be prescribed to about 10 percent of those non-adults thought to have bipolar disorder.
While not recommended, one half of all those assessed as being bipolar are prescribed antidepressants, such as SSRIs, as first line treatment. It has been suggested that this class of drugs has decreased the risk of suicide attempts compared with other classes of antidepressants for close to 20 years. Yet tricyclic antidepressants have been determined to be efficacious in over half of those diagnosed with bipolar disorder- with a greater amount of research behind this class of drugs. Yet, entirely recognized treatments for bipolar disorder long term are lithium or lamictal- along with an anti-convulsant. Sugar intake is thought to vex the symptoms of one with a bipolar disorder as well.
Atypical anti-psychotics have been prescribed for bipolar disorder, which change some aspects of the brain, physiologically, as does the disease itself. In fact, one may argue the brain becomes more efficient due to both the disorder and the treatment with the atypical anti-psychotics. Yet many recommend the utilization of this class of drugs with bipolar disorder only if psychosis is present as well. As many as 15 percent of bipolar disorder patients diagnosed as such are prescribed an atypical presently. This class of medications may be particularly beneficial for those women who are diagnosed with bipolar disorder who are pregnant, however.
Lithium, which is essentially a very light metal with low density in which the salts are obtained for medicinal treatment, and an anti-convulsant are believed to be standard bipolar treatment, pharmacologically, studies have shown. This is due to Dr. John Cade and his examination with lithium and its benefits with those who have psychotic excitement close to 60 years ago. Lithium is believed to be both neuro-protective as well as having an anti-suicidal affect in those believed to be bipolar- and is viewed as a mainstay as far as treatment for bipolar goes with many who treat the disorder. Lithium is thought to regulate the calcium molecule in the brain, so this and valporate are historically the medicinal treatment options preferred for those with bipolar disorder.
Bipolar is difficult to detect, and is often diagnosed as major depression with many affected by this disorder. There is no objective criteria protocol available to utilize when assessing any patient believed to be suffering from any mental disorder. So such mental disorders that are diagnosed are ambiguous, yet that does not conclude that such disorders do not exist, such as the case with bipolar disorder.
Yet perhaps a health care provider should be very thorough and knowledgeable when assessing a patient believed to have a mental condition such as bipolar disorder,
Dan Abshear
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