Limbic Intrinsic Connectivity in Depressed and High-Risk Youth

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.

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.

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).

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.