Content

People with bipolar disorder suffer from excessive emotional highs and lows that can cycle uncontrollably, severely distorting their awareness of self and others, impairing social and work ability and causing high risk of suicide. Current treatments are only partly effective. Researchers at Baylor College of Medicine have used mouse models and advanced molecular mapping studies in both mouse and human to learn how a gene associated with bipolar disorder controls the balance between brain excitation and inhibition and shown for the first time that it also is linked to epilepsy.

The findings, appearing recently in the early online edition of Molecular Psychiatry, open new treatment strategies for both bipolar disorder and epilepsy.

“We became very interested in a gene called ankyrin 3, or ANK3, a decade ago when we discovered it coded for a partner of two other genes that are mutated in some people with epilepsy. Soon afterward, ANK3 was connected with bipolar disorder by genetic testing of thousands of psychiatric patient volunteers around the world,” said Dr. Edward C. Cooper, associate professor of neurology, molecular and human genetics, and neuroscience at Baylor. “Although there are important differences, we noted similarities between bipolar disorder and epilepsy: both cycle, both are risk factors for the other, and both are currently treated using many of the same drugs. Reasons behind these overlaps were mysterious, and the specific parts of the ANK3 gene linked with bipolar had no known function. We decided to take a much closer look at the human brain and mice with bipolar-like behavior. In our study we found that reduced expression of one type of ANK3 removes a brake on the output of brain neurons, leading to excesses in firing in circuits for emotions, memory and epilepsy.”