Person:

Bogdan, Ryan

Background. Anhedonia and stress sensitivity have been identified as promising depressive phenotypes. Research suggests that stress-induced anhedonia is a possible mechanism underlying the association between stress and depression. The present proof-of-concept study assessed whether hedonic capacity and stress perception are heritable and whether their genetic and environmental contributions are shared. Method. Twenty monozygotic (MZ) and 15 dizygotic (DZ) twin pairs completed a probabilistic reward task that provides an objective behavioral measure of hedonic capacity (reward responsiveness) and completed several questionnaires including the Perceived Stress Scale (PSS). Bivariate Cholesky models were used to investigate whether covariation between (1) depressive symptoms and hedonic capacity, (2) depressive symptoms and perceived stress, and (3) perceived stress and hedonic capacity resulted from shared or residual genetic and environmental factors. Results. Additive genetic (A) and individual-specific environment (E) factors contributed to 46% and 54% of the variance in hedonic capacity, respectively. For perceived stress, 44% and 56%, of the variance was accounted for by A and E factors, respectively. The genetic correlation between depression and hedonic capacity was moderate (r(a)=0.29), whereas the correlation between depression and stress perception was large (r(a)=0.67). Genetic and environmental correlations between hedonic capacity and stress perception were large (r(a)=0.72 and r(e)= -0.43). Conclusions. The present study provides initial feasibility for using a twin approach to investigate genetic contributions of a laboratory-based anhedonic phenotype. Although these preliminary findings indicate that hedonic capacity and perceived stress are heritable, with substantial shared additive genetic contributions, replications in larger samples will be needed.

Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity, in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the decree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression.

Major depressive disorder (MDD)is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic punishment learning task. Despite equivalent behavioral performance, RD participants showed larger feedback-related negativities to negative feedback relative to controls; group differences remained after accounting for residual anxiety and depressive symptoms. The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms.