Validating Psychosocial Pathways of Risk Between Neuroticism and Late Life Depression Using a Polygenic Score Approach

Neuroticism is a stable and heritable personality trait that is strongly linked to depression. Yet, little is known about its association with late life depression, as well as how neuroticism eventuates into depression. This study used data from the Wisconsin Longitudinal Study (WLS; N = 4,877) to examine the direct and indirect effects of neuroticism on late life depression at 3 points in the life course-ages 53, 64, and 71-via stressful life events (i.e., independent and dependent) and social supports measured across adulthood and into later life. Neuroticism was assayed using multiple methods, including self-report measures (phenotypic model) and a polygenic score (polygenic model) informed by a meta-analytic genome-wide association study. Results indicated that the phenotypic model of neuroticism and late life depression was partially mediated via dependent stressful life events experienced after the age of 53 and by age 64 social support. This association was replicated in the polygenic model of neuroticism, providing key evidence that the findings are robust. No indirect effects emerged with respect to age 53 social support, age 71 social support, adult dependent stressful life events (experienced between age 19 and 52), and adult and late life independent stressful life events in either the phenotypic or polygenic models as they pertained to late life depression. Results are consistent with previous findings that individuals with high neuroticism may be vulnerable to late life depression through psychosocial risk factors that are, in part, attributable to their own personality.