Andrew M. McIntosh, M.D., Chair of Biological Psychiatry at the University of Edinburgh, U.K., used his 2010 NARSAD Independent Investigator Grant to probe whether abnormalities in white matter integrity associated with mood disorders (bipolar disorder or BD and major depressive disorder or MDD) can be linked to genetic risk for these illnesses. More than 350 million people of all ages suffer from depression (including both BD and MDD) worldwide, according to the World Health Organization, and it is the leading cause of global disability. Dr. McIntosh and colleagues’ research aims to establish a more precise biological risk profile for these illnesses to facilitate early detection and intervention.

The research team identified a crucial correlation between mood disorder risk genes and a specific biological trait that can be seen in functional brain imaging studies. The trait has to do with what scientists call the “integrity” of the brain’s connections (i.e., white matter). An overall risk score reflecting the accumulation of multiple mood disorder genes was determined for individuals who were not ill but had a close relative with bipolar disorder. This mood disorder risk score was found to correlate with reduced white matter integrity, viewed via brain scan.

The findings, published online in Biological Psychiatry on March 4, 2013, support the hypothesis that vulnerability to depression is caused by malfunctioning circuitry in the brain, where impaired connectivity contributes to the development of mood disorder. The results further indicate a genetic origin of these deficits, offering the potential to identify specific biological pathways involved in the illness and to develop more precise treatment options for those affected.