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. 2018 Oct;57(10):775-785.e3.
doi: 10.1016/j.jaac.2018.06.017. Epub 2018 Aug 16.

Limbic Intrinsic Connectivity in Depressed and High-Risk Youth

Manpreet K Singh  1 , Sara M Leslie  2 , Mary M Packer  2 , Elizabeth F Weisman  2 , Ian H Gotlib  3
Affiliations

Limbic Intrinsic Connectivity in Depressed and High-Risk Youth

Manpreet K Singh et al. J Am Acad Child Adolesc Psychiatry. 2018 Oct.

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.

Keywords: family history; limbic; pediatric depression; resting state; risk.

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Figures

FIGURE 1
FIGURE 1
Significant Between-Group Differences in Average Resting-State Functional Connectivity Between the Amygdala Seed and the Right Superior and Middle Frontal Gyri (A), Precuneus (B), Left Lingual and Fusiform Gyri (C), and Right Lingual and Fusiform Gyri (D) Note: Graphs show the mean differences for the depressed (DEP), familial-risk (DEP-Risk), and healthy control (HC) groups. Error bars are standard errors of the mean. n.s. = not significant; RSFC = resting state functional connectivity. Please note color figures are available online. *p < .05, ** p < .01, *** p < .001.
FIGURE 2
FIGURE 2
Significant Between-Group Differences in Average Resting-State Functional Connectivity Between the Nucleus Accumbens Seed and the Left Superior Frontal Gyrus (A), Right Insula (B), and Left Insula (C) Note: Graphs show the mean differences for the depressed (DEP), familial-risk (DEP-risk), and healthy control (HC) groups. Error bars are standard errors of the mean. NAcc = nucleus accumbens; n.s. = not significant; RSFC = resting state functional connectivity. Please note color figures are available online. * p < .05, ** p < .01, *** p < .001.
FIGURE 3
FIGURE 3
Correlation Scatterplots Between Age, Sex, and IQ-Adjusted Connectivity Estimates Depression Severity in Youth With Depressive Disorders Note: NAcc = nucleus accumbens. Please note color figures are available online.
See this image and copyright information in PMC

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