Polygenic risk for depression and resting state functional connectivity of subgenual anterior cingulate cortex in young adults

Abstract

Genetic variants may confer risks for depression by modulating brain structure and function. Prior evidence has underscored a key role of the subgenual anterior cingulate cortex (sgACC) in depression. Here, we built on the literature and examined how the resting state functional connectivity (rsFC) of the sgACC was associated with polygenic risks for depression. We followed published routines and computed seed-based whole-brain sgACC rsFC and polygenic risk scores (PRS) of 717 young adults curated from the Human Connectome Project. We performed whole-brain regression against PRS and severity of depression symptoms in a single model for all subjects and for men and women alone, controlling for age, sex (for all), race, severity of alcohol use, and household income, and evaluated the results at a corrected threshold. We found lower sgACC rsFC with the default mode network and frontal regions in association with PRS and lower sgACC-cerebellar rsFC in association with depression severity. We also noted sex differences in the connectivity correlates of PRS and depression severity. In an additional set of analyses, we observed a significant correlation between PRS and somatic complaints score and altered sgACC-somatosensory cortical connectivity in link with the severity of somatic complaints. Our findings collectively highlighted the pivotal role of distinct sgACC-based networks in the genetic predisposition to depression and the clinical manifestation of depression. Distinguishing the risk from severity markers of depression may have implications in developing early and effective treatments for individuals at risk for depression.