Scientists Link Bipolar Disorder to Unexpected Brain Region

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A painted black brain on a rainbow background. Credit to flickr.com user Anders Sandberg. Used with permission under a Creative Commons license.

While bipolar disorder is one of the most-studied neurological disorders—the Greeks noticed symptoms of the disease as early as the first century—it’s possible that scientists have overlooked an important part of the brain for its source.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown for the first time that ensembles of genes within the striatum—a part of the brain that coordinates many primary aspects of our behavior, such as motor and action planning, motivation, and reward perception—could be deeply involved in the disorder. Most modern studies of bipolar disorder have concentrated on the brain’s cortex, the largest part of the brain in humans, associated with higher-level thought and action.

“This is the first real study of gene expression in the striatum for bipolar disorder,” said Ron Davis, chair of the Department of Neuroscience at TSRI, who directed the study. “We now have a snapshot of the genes and proteins expressed in that region.”

The study, published recently online ahead of print in the journal Molecular Psychiatry, also points to several pathways as potential targets for treatment.

Bipolar disorder is a mental illness that affects about 2.6 percent of the U.S. adult population—some 5.7 million Americans—with a sizable majority of these cases classified as severe. The disease runs in families, and more than two-thirds of people with bipolar disorder have at least one close relative with the illness or with unipolar major depression, according to the National Institute of Mental Health.

In the new research, tissue samples from 35 bipolar and non-bipolar control subjects were analyzed. The number of genes differentially expressed in tissue samples from the two groups turned out to be surprisingly small—just 14 in all. However, co-expression network analysis also revealed two modules of interconnected genes that were particularly rich in genetic variations associated with bipolar disorder, suggestive of a causal role in the disorder. One of these two modules was particularly striking, as it seemed to be highly specific to the striatum.

“Our finding of a link between bipolar disorder and the striatum at the molecular level complements studies that implicate the same brain region in bipolar disorder at the anatomical level, including functional imaging studies that show altered activity in the striatum of bipolar subjects during tasks that involve balancing reward and risk,” said TSRI Research Associate Rodrigo Pacifico, who was first author of the new study. Analyzing reactions to risk was important because bipolar patients may act impulsively and engage in high-risk activities during periods of mania.

Pathway analysis also found changes in genes linked to the immune system, the body’s inflammatory response, and cells’ energy metabolism. Davis noted, “We don’t know if these changes are a cause of the disease or the result of it. But they provide additional gene markers in bipolar disorder that could potentially lead to the future development of diagnostics or treatments.”

The study, “Transcriptome Sequencing Implicates Dorsal Striatum-Specific Gene Network, Immune Response and Energy Metabolism Pathways in Bipolar Disorder,” was supported by funding from the State of Florida.

Text</a< from the Scripps Research Institute.

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Treatable Condition Could be Mistaken for Bipolar Disorder

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Credit to the NIH Image Gallery on flickr.com. Used with permission under a Creative Commons license.

Researchers at Houston Methodist will pioneered a new study that will hopefully show that a significant number of people may have a treatable immune system condition often mistaken for either bipolar disorder or schizophrenia. This study could impact millions of people.

“We suspect that a significant number of people believed to have schizophrenia or bipolar disorder actually have an immune system disorder that affects the brain’s receptors,” said Joseph Masdeu, M.D., Ph.D., the study’s principal investigator and a neurologist with the Houston Methodist Neurological Institute. “If true, those people have diseases that are completely reversible – they just need a proper diagnosis and treatment to help them return to normal lives.”

In 2007, scientists discovered anti-NMDA receptor encephalitis, a disease which can be treated with immunotherapy medications that causes symptoms similar to bipolar disorder or schizophrenia. The encephalitis forces the immune system to attack N-methyl-D-aspartate (NMDA) receptors in the brain instead of invading agents.

The NMDA receptors control decision-making, thoughts, and perceptions, which is why this illness is often mistaken for bipolar disorder or schizophrenia. The encephalitis can also cause sufferers to hear voices or become paranoid.

The study will collect cerebral spinal fluid from 150 patients diagnosed with bipolar disorder or schizophrenia and 50 healthy controls between the ages of 18 to 35. The fluid will be examined for antibodies attacking NMDA and other brain receptors. If abnormal antibodies are found, the researchers will notify the patient so he or she may consider treatment.

Masdeu plans to use the findings for development of further studies about antibodies.

Materials provided by Houston Methodist.

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Depression Changes Our Language

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Depression. A pit of despair for many people. Scientists have attempted to pin down the relationship between depression and language for a long time now, and technology has just given researchers the breakthrough they needed.

In the past, field studies were carried out by scientists who took notes on what people said. Now, computers can analyze banks of data in seconds, picking up on patterns that a human analyst might miss. Researchers fed personal essays, diary entries, and blog posts to their computers and found some interesting patterns in the language of people suffering from depression.

It should come as no surprise that people who deal with depression use more negative language, with words such as “lonely,” “sad,” and “miserable.” But what surprised the scientists was the use of first-person pronouns, such as “I,” “myself,” and “me.” People who suffer from depression apparently don’t use very many second- and third-person pronouns, such as “you,” “they,” and “them,” indicating that depression is a self-focused disease. Researchers found that the pronoun usage was more indicative of depression than the negative language.

However, on an examination of 64 different forums, absolutist language, using words such as “always,” “never,” and “completely,” was a better indicator of mental health issues than negative language or pronouns. On suicidal ideation forums, the use of absolutist language was 80% greater than language used by 19 control forums. This shows that people who suffer from depression have a black-and-white outlook.

Scientists hope that computers will soon be able to classify mental disorders from blog posts. Such classification is already outperforming trained therapists.

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New Research Pinpoints Bipolar Disorder Gene

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Credit to flickr.com user Berkeley Lab. Used with permission under a Creative Commons license.

A new study published in the Molecular Psychiatry journal reports that researchers have found a mutation in a gene that causes bipolar disorder in as many as ten percent of cases. This is fantastic news! Finally, the causes of bipolar disorder are starting to be pinpointed.

The gene, G protein receptorkinase 3 (GRK3), regulates neurotransmitters such as dopamine. The mutation happens in a section of the gene called the promoter, which turns GRK3 on and off. Scientists at the University of California, San Diego (UCSD) School of Medicine hypothesize that what causes bipolar disorder is that the mutation makes the gene hypersensitive to dopamine.

The study took place over a year, and screened DNA samples from more than 400 families with bipolar disorder. The researchers found six mutations in the promoter region of GRK3. Most notable was that the P-5 mutation happened three times more frequently in people who suffer from bipolar disorder than those who don’t.

Research has long pointed to several genes being the causes of bipolar disorder. But this is the first time a single gene has been determined as a cause. Bipolar disorder is characterized by extreme highs and lows. Few therapies work to treat the mental illness, and those that do work aren’t effective for all people who suffer from it. The scientists involved in this study hope that specific therapies that target genes on a molecular level will be developed.

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