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UCLA researchers searching for genes that cause bipolar disorder

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Bipolar disorder is a severe mental illness that affects 1-2% of the population. Although it is known that genetic factors are significantly involved in the disorder, the specific genes that are responsible are not known. Therefore, UCLA researchers have developed a new approach to identify these genes. They published their findings on February 12 in the journal JAMA psychiatry.

The standard method for determining whether an individual suffers from bipolar disorder is a standard clinical interview; however, in addition to using this technique, the researchers combined the results from brain imaging, cognitive testing, and a variety of temperament and behavior measurements. Using the new method, UCLA researchers, together with colleagues from UC San Francisco, Colombia’s University of Antioquia, and the University of Costa Rica, determined approximately 50 brain and behavioral measurements, which are both under significant genetic control and associated with bipolar disorder. They note that their findings could be significantly helpful for identifying the specific genes that contribute to the illness.

Bipolar disorder causes major shifts in mood and energy; thus, it interferes with the ability to carry out everyday tasks. Individuals suffering from bipolar disorder experience tremendous highs and extreme lows; when they are in the low phase, they do not even want to get out of bed. The genetic causes of bipolar disorder are extremely complex and probably involve many different genes, explained senior author Carrie Bearden, an associate professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior. She noted, “The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder. This is an innovative approach to identifying genetically influenced brain and behavioral measures that are more closely tied to the underlying biology of bipolar disorder than the clinical symptoms alone are.”

The study group comprised 738 adults; 181 of them suffered from severe bipolar disorder. They underwent high-resolution 3-D images of the brain, completed questionnaires that evaluated temperament and personality traits of individuals diagnosed with bipolar disorder and their non-bipolar relatives, and completed an extensive battery of cognitive tests that assessed long-term memory, attention, inhibitory control, and other neurocognitive abilities. The researchers found that approximately 50 of these measurements exhibited strong evidence of being influenced by genetics. Of particular significance was the discovery that the thickness of the gray matter in the brain’s temporal and prefrontal regions, which are the structures that are critical for language and for higher-order cognitive functions such as self-control and problem-solving, were the most promising candidate traits for genetic mapping; this was based on both their strong genetic component and association with the disease. Dr. Bearden explained, “These findings are really just the first step in getting us a little closer to the roots of bipolar disorder. What was really exciting about this project was that we were able to collect the most extensive set of traits associated with bipolar disorder ever assessed within any study sample. These data will be a really valuable resource for the field.”

The study group all were members of large families living in Costa Rica’s central valley and Antioquia, Colombia. Approximately 400 years ago, the families were founded by European and native Amerindian populations; they were chosen for the study because they have remained fairly isolated since their founding; thus, their genetics are simpler for researchers to study, compared to those of general populations. The researchers found that their findings were similar to those reported in previous, smaller studies of other populations. Dr. Bearden said, “This suggests that even if the specific genetic variants we identify may be unique to this population, the biological pathways they disrupt are likely to also influence disease risk in other populations.”

The next phase of this research is to use the genomic data they collected from the families, including full genome sequences and gene expression data, to begin identifying the specific genes that contribute to the risk of bipolar disorder. In addition, the researchers plan to extend their assessment into the children and teens in these families. They theorize that many of the bipolar-related brain and behavioral differences found in adults with bipolar disorder have their origins in adolescent neurodevelopment.

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