Abstract

BACKGROUND: Characterizing (1) functional connectivity (FC) markers of risk and resilience in emotion and reward networks and (2) how family dynamics in youth at high familial risk for bipolar disorder (HR-BD) and major depressive disorder (HR-MDD) are related to FC may advance our understanding of the neural underpinnings of mood disorders and lead to more effective interventions.METHODS: 139 youth (43 HR-BD, 46 HR-MDD, and 50 low risk [LR]) aged 12.9+/-2.7 years were followed for 4.5+/-2.4 years. We characterized differences in striato-limbic FC that distinguished HR-BD, HR-MDD and LR; and resilience (RES) versus conversion to psychopathology (CVT). We then examined whether risk status moderated FC-family function associations. Finally, we examined whether baseline differences in FC between HR-BD, HR-MDD and LR predicted RES versus CVT at follow-up.RESULTS: HR-BD had greater amygdala-middle frontal gyrus and dorsal striatum-middle frontal gyrus FC, and HR-MDD had lower amygdala-fusiform gyrus and dorsal striatum-precentral gyrus FC (voxel-level p<0.001, cluster-level FDR-corrected p<0.05). RES had greater amygdala-orbitofrontal cortex and ventral striatum-dorsal anterior cingulate cortex FC relative to CVT (voxel-level p<0.001, cluster-level FDR-corrected p<0.05). Greater family rigidity was inversely associated with amygdala-fusiform gyrus FC across all groups (FDR-corrected p=0.017), with a moderating effect of bipolar risk status (HR-BD vs. HR-MDD p<0.001; HR-BD versus LR p=0.005). Baseline FC differences did not predict RES versus CVT.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.

View details for DOI 10.1016/j.bpsc.2022.02.009

View details for PubMedID 35272095