UC Davis

BACKGROUND: Few studies to date have characterized functional connectivity (FC) within emotion and reward networks in relation to family dynamics in youth at high familial risk for bipolar disorder (HR-BD) and major depressive disorder (HR-MDD) relative to low-risk youth (LR). Such characterization may advance our understanding of the neural underpinnings of mood disorders and lead to more effective interventions. METHODS: A total of 139 youth (43 HR-BD, 46 HR-MDD, and 50 LR) aged 12.9 ± 2.7 years were longitudinally followed for 4.5 ± 2.4 years. We characterized differences in striatolimbic FC that distinguished between HR-BD, HR-MDD, and LR and between resilience and conversion to psychopathology. We then examined whether risk status moderated FC-family dynamic associations. Finally, we examined whether baseline between-group FC differences predicted resilence versus conversion to psychopathology. RESULTS: HR-BD had greater amygdala-middle frontal gyrus and dorsal striatum-middle frontal gyrus FC relative to HR-MDD and LR, and HR-MDD had lower amygdala-fusiform gyrus and dorsal striatum-precentral gyrus FC relative to HR-BD and LR (voxel-level p < .001, cluster-level false discovery rate-corrected p < .05). Resilient youth had greater amygdala-orbitofrontal cortex and ventral striatum-dorsal anterior cingulate cortex FC relative to youth with conversion to psychopathology (voxel-level p < .001, cluster-level false discovery rate-corrected p < .05). Greater family rigidity was inversely associated with amygdala-fusiform gyrus FC across all groups (false discovery rate-corrected p = .017), with a moderating effect of bipolar risk status (HR-BD vs. HR-MDD p < .001; HR-BD vs. LR p = .005). Baseline FC differences did not predict resilence versus conversion to psychopathology. CONCLUSIONS: Findings represent neural signatures of risk and resilience in emotion and reward processing networks in youth at familial risk for mood disorders that may be targets for novel interventions tailored to the family context.