Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression

IntroductionMajor depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals.MethodsIn this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI.ResultsAcross groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=−0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences.LimitationSmall sample size, which warrants replication.ConclusionDepressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression.