Rather than just relying on clinical symptoms alone, researchers combined the findings of brain imaging, cognitive testing, and a variety of temperament and behavior tests to identify about 50 brain and behavioral measures that have both a strong genetic influence and a link to bipolar disorder.
“The genetic causes of bipolar disorder are highly complex and likely involve many different genes,” said Carrie Bearden, Ph.D., a senior author of the study and an associate professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior.
“The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder,” Bearden said.
“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 involved 738 adults, 181 of whom were diagnosed with severe bipolar disorder. The researchers took high-resolution 3-D images of their brains and gave questionnaires that measured temperament and personality traits to those diagnosed with bipolar disorder and their non-bipolar relatives. They also conducted a wide variety of cognitive tests assessing long-term memory, attention, inhibitory control, and other neurocognitive skills.
Approximately 50 of these measures showed strong evidence of being influenced by genetics. Of particular interest was the discovery that the thickness of gray matter in the brain’s temporal and prefrontal regions looked the most promising for potential genetic mapping, based on both its strong genetic basis and its link to bipolar.
“These findings are really just the first step in getting us a little closer to the roots of bipolar disorder,” Bearden said. “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. This data will be a really valuable resource for the field.”
Next, the researchers hope to use the genomic data they collected from the families — including full genome sequences and gene expression data — to identify the specific genes that contribute to risk for bipolar disorder.
The researchers also plan to extend their research to include the children and teens in these families. They hypothesize that many of the bipolar-related brain and behavioral symptoms found in bipolar adults had their origins in adolescent neurodevelopment.
The results are published in the journal JAMA Psychiatry.