Polygenic Risks for Depression and Neural Responses to Reward and Punishment in Young Adults

Abstract

Background: Extensive research has shown aberrant reward and punishment processing in people with depression. Genetic risks contribute to depression, but whether or how these risks of depression may affect behavioral and neural responses to reward and punishment remains unclear. Methods: We curated the data of 879 young adults performing a gambling task during brain imaging from the Human Connectome Project. Depression severity was assessed with the Achenbach Adult Self Report. Polygenic risk scores (PRSs) for depression were computed for all participants. With published routines and at a corrected threshold, we evaluated how brain responses to reward and punishment were associated with depression scores and PRSs in a linear regression in all, male, and female participants, with age, sex (for all), race, and drinking severity as covariates. Results: The results showed broad frontal, parietal, and occipital cortical activation in negative correlation with PRSs during both reward and punishment processing. Notably, posterior cingulate cortical activation was specifically associated with PRS-related punishment processing. In addition, men and women displayed both shared and distinct neural responses to PRS-related reward and punishment processing. Conclusions: These findings highlight the influence of genetic risks for depression on neural responses to reward and punishment and provide insights into genetically informed markers of depression.