Bipolar disorder’s effects on mood may stem from a suite of genetic risks which together cause brain circuit changes that increase vulnerability to the disorder, new research suggests.

It’s well-established that the accumulation of “risk” genes – which scientists call genetic risk-variants -- contributes substantially to bipolar disorder (BD). Many studies have focused on identifying single genetic risks that increase the risk of developing BD. In the new study, published in the journal Neuroimage: Clinical, researchers found that adults with the disorder who score higher on a measure of their cumulative genetic risk for BD (called a BD polygenic risk score) were more likely to display abnormal brain activity associated with vulnerability to BD. Adult BD patients, unaffected relatives, and unrelated healthy people were included in the study.

All four of the scientists on the team are Young Investigator grantees. Danai Dima, Ph.D., and Simone de Jong, Ph.D., each received a grant in 2014; and Gerome Breen, Ph.D., received one in 2007. Senior author Sophia Frangou, M.D., Ph.D., also received an Independent Investigator grant in 2008 after being a Young Investigator grantee in 2002.

Study participants performed a facial recognition task, which revealed that people who had a higher polygenic BD risk score showed less activity in the region of the brain that processes visual information. The researchers suggest that this and other abnormalities in the recruitment of brain circuits key to processing emotional information may contribute to poor emotional regulation.

In tasks related to the processing of working memory—the type of memory used to complete immediate tasks, such as making a decision—higher genetic risk scores were correlated with more activity in a brain region involved in processing emotional information. This area normally becomes less active while engaged in a task.

Scoring the study participants’ genetic risk for BD was most informative for identifying patterns of activity in the brain that predispose individuals to the disorder, the researchers say. This approach was not as effective, however, for identifying patterns in the way the symptoms of actual BD patients were expressed. The researchers hope that further mapping of the effects of genetic BD risks will enable them to identify brain circuit abnormalities characteristic of the disorder.