Neural correlates of emotion processing predict resilience in youth at familial risk for mood disorders

Aberrant face emotion processing has been demonstrated in youth with and at a familial risk for bipolar and major depressive disorders. However, the neurobiological factors related to emotion processing that underlie resilience from youth-onset mood disorders are not well understood. Functional magnetic resonance imaging data during an implicit emotion processing task were collected at baseline from a sample of 50 youth, ages 8-17, who were healthy but also familially at high risk for either bipolar disorder or major depressive disorder, and 24 healthy controls with no family history of psychopathology (HCL). Participants were reevaluated 3 years later and classified into three groups for analysis: high-risk youth who converted to a psychiatric diagnosis (CVT; N = 23), high-risk youth who were resilient from developing any psychopathology (RES; N = 27), and HCL youth (N = 24) who remained healthy at follow-up. For happy > calm faces, the CVT and RES groups had significantly lower activation in the left inferior parietal lobe (IPL), while the RES group had lower activation in the right supramarginal gyrus. For fear > calm faces, the RES group had lower activation in the right precuneus and inferior frontal gyrus (IFG) compared to the CVT group. Connectivity analyses revealed the RES group exhibited higher left IPL connectivity with visual cortical regions for happy > calm faces, and higher IFG connectivity with frontal, temporal, and limbic regions for fear > calm faces. These connectivities were correlated with improvements in prosocial behaviors and global functioning. Our findings suggest that differential activation and connectivity in the IPL, IFG, and precuneus in response to emotional stimuli may represent distinct resilience and risk markers for youth-onset mood disorders.