Neuroticism and reward-related ventral striatum activity: Probing vulnerability to stress-related depression

Background: Elevated neuroticism may confer vulnerability to the depressogenic effects of stressful life events (SLEs). Vulnerability to stress-related disruption of neural reward processing is a promising neural mechanism undergirding links between stress and depression. Methods: Data came from 2 studies: the St. Louis Personality and Aging Network (SPAN) study and the Duke Neurogenetics Study (DNS). In SPAN, we used longitudinal self-reported data from older adults (n=971) to examine whether neuroticism moderates the association between recent stressful life events and subsequent depressive symptoms. In the DNS, we tested whether this interaction is present among young adult college students (n=1,343), and further whether neuroticism moderates the association between SLEs and reward-related ventral striatum activation as measured using functional magnetic resonance imaging (n=1,195).Results: In SPAN, SLEs prospectively predicted future depressive symptoms, especially among those reporting elevated N, even after accounting for prior depressive symptoms and previous SLE exposure (NxSLE interaction: p=0.016, ΔR2=0.003). In Study 2, we replicated this effect (NxSLE interaction: p=0.019, ΔR2=0.003). Further, neuroticism moderated the association between SLEs and reward-related left VS activity such that individuals with high neuroticism who were also exposed to more SLEs had blunted reward-related left VS activation (NxSLE: p=0.017, ΔR2=0.0048) which was associated with a lifetime depression diagnosis (r=-0.07, p=0.02), but not current depressive symptoms (r=-0.003, p=0.93).Conclusions: These data suggest that neuroticism may promote vulnerability to stress-related depression, and that sensitivity to stress-related VS dysfunction may be a potential neural mechanism underlying vulnerability to stress-related clinically significant depression.