Abstract

OBJECTIVE: Depression runs in families and has been associated with dysfunctional limbic connectivity. Whether aberrant limbic connectivity is a risk factor for or a consequence of depression is unclear. To examine this question, we compared resting state functional connectivity (RSFC) in youth with depressive disorders (DEP), healthy offspring of parents with depression (DEP-risk), and healthy comparison (HC) youth.METHOD: Magnetic resonance imaging at rest was acquired from 119 youth, aged 8 to 17 years (DEP, n= 41, DEP-risk, n= 39, and HC, n= 39) and analyzed using seed-based RSFC in bilateral amygdala and nucleus accumbens (NAcc), covarying for age, IQ, and sex.RESULTS: We found distinct risk- and disorder-specific patterns of RSFC across groups. DEP-risk and DEP youth shared reduced negative amygdala-right frontal cortex RSFC and reduced positive amygdala-lingual gyrus RSFC compared to HC youth (p< .001). DEP-risk youth had weaker negative amygdala-precuneus RSFC compared to DEP and HC youth (p< .001), suggesting a resilience marker for depression. In contrast, DEP youth had increased positive NAcc-left frontal cortex RSFC and reduced positive NAcc-insula RSFC compared to DEP-risk and HC youth (p<.001), suggestive of disorder-specific features of depression. Greater depression severity was correlated with disorder-specific amygdala and NAcc RSFC (p< .05).CONCLUSION: RSFC in the amygdala and NAcc may represent selective disorder- and risk-specific markers in youth with, and at familial risk for, depression. Longitudinal studies are needed to determine whether these patterns predict long-term clinical outcomes.

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