Researchers at UCLA took a new approach to identify genes that may contribute to bipolar disorder. Instead of using only a standard clinical interview to determine whether or not individuals met the criteria for a clinical diagnosis, the researchers combined the results from brain imaging, cognitive testing and an array of temperament and behavior measures. Using the new method, the investigators — in collaboration with others at UC San Francisco, Colombia’s University of Antioquia and the University of Costa Rica — identified about 50 brain and behavioral measures that are both under strong genetic control and associated with bipolar disorder.
“The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder,” says Carrie Bearden, PhD, associate professor of psychiatry and psychology at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. “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 are the clinical symptoms alone.”
The researchers used high-resolution 3-D images of the brains of 738 adults, 181 of whom have severe bipolar disorder; questionnaires evaluating temperament and personality traits of individuals diagnosed with bipolar disorder and their non-bipolar relatives; and an extensive battery of cognitive tests assessing long-term memory, attention, inhibitory control and other neurocognitive abilities. Approximately 50 of these measures showed strong evidence of being influenced by genetics. “These findings are really just the first step in getting us a little closer to the roots of bipolar disorder,” Dr. Bearden says. “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.”
Individuals in the study are members of large families living in Costa Rica’s central valley and Antioquia, Colombia, with a very high incidence of bipolar disorder. The groups were chosen because they have remained fairly isolated, and their genetics are therefore simpler for scientists to study than those of general populations. The fact that the findings aligned closely with those of previous, smaller studies in other populations was surprising even to the scientists, given the subjects’ unique genetic backgrounds and living environments.
“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,” Dr. Bearden says.
The researchers’ next step is to use the genomic data collected from the families — including full genome sequences and gene-expression data — to begin identifying the specific genes that contribute to risk for bipolar disorder. The researchers also plan to extend their investigation into the children and teens in these families.
“Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees,” JAMA Psychiatry, February 12, 2014