Reward Functioning Abnormalities in Adolescents at High Familial Risk for Depressive Disorders

Abstract Background A parental history of major depressive disorder (MDD) is an established risk factor for youth MDD and clarifying the mechanisms related to familial risk transmission is critical. Aberrant reward processing is a promising biomarker of MDD risk; accordingly, the aim of the current study was to test behavioral measures of reward responsiveness and underlying frontostriatal resting activity in healthy adolescents, both with (high-risk) and without (low-risk) a maternal history of MDD. Methods Low-risk and high-risk 12-14-year-old adolescents completed a probabilistic reward task (n = 74 low-risk, n = 27 high-risk) and a resting state MRI scan (n = 61 low-risk, n = 25 high-risk). Group differences in response bias toward reward and resting ventral striatal (VS) and medial prefrontal cortex (mPFC) fractional amplitude of low frequency fluctuations (fALFF) were examined. Computational modeling was applied to dissociate reward sensitivity versus learning rate. Results High-risk adolescents showed a blunted response bias compared to low-risk adolescents. Computational modeling analyses revealed that, relative to low-risk adolescents, high-risk adolescents exhibited reduced reward sensitivity but similar learning rate. Although there were no group differences in VS and mPFC fALFF, groups differed in relationships between mPFC fALFF and response bias. Specifically, among high-risk adolescents, higher mPFC fALFF correlated with a blunted response bias, whereas there was no fALFF-response bias relationship among low-risk youth. Conclusion High-risk adolescents exhibit reward functioning impairments, which is associated with mPFC fALFF. The blunted response bias-mPFC fALFF association may reflect an excessive mPFC-mediated suppression of reward-driven behavior, which may potentiate MDD risk.