Limbic Intrinsic Connectivity in Depressed and High-Risk Youth
Open accessAbstract
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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Relative to healthy children, children at increased vulnerability due to parental major depressive disorder history, as well as children with current major depressive disorder, had lower resting state functional connectivity between the right dorsolateral prefrontal cortex and the amygdala.
“Thus, relative to healthy children (8-17 years old), children at increased vulnerability due to parental MDD history (as well as children with current MDD) had lower rsFC between the right dlPFC (BA6/8/9) and the amygdala [74]”
From Prefrontal cortex and depression (2022) · cites this paper as [74]
The Results (Group Differences in Amygdala RSFC; page unavailable) report reduced negative amygdala–right frontal connectivity in both the at-risk and depressed groups relative to healthy youth. However, the measured frontal cluster included the superior and middle frontal gyri and frontal pole (BAs 6, 8, 9, and 32), rather than being identified solely as the right dlPFC. The Participants and Participant Characteristics sections also show that the depressed group included youth with dysthymia or unspecified MDD, so the result was not reported specifically for children with current MDD. (LLM, conf=0.88)
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Prefrontal cortex and depression
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- Authors
- Singh, M. K., Leslie, S. M., Packer, M. M., Weisman, E. F., & Gotlib, I. H.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Corresponding author
- Singh, Manpreet K.
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 57
- Issue
- 10
- Pages
- 775-785.e3
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC11890206
- OpenAlex
- W2887306654
- Cited by
- 54
- References
- 74
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 27 · 2020: 3 · 2019: 3 · 2018: 1
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (MH085919, MH106581, MH101495)
- Stanford Child Health Research Institute
- NIMH
- National Institute of Aging
- Neuronetics
- Johnson and Johnson
- Brain and Behavior Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- adolescent depression, familial risk for depression, resting-state functional connectivity, limbic system, amygdala, nucleus accumbens, precuneus, insula, depression severity, offspring of depressed parents
- MeSH terms
- Adolescent, Amygdala, Brain Mapping, Cerebral Cortex, Child, Depression, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neural Pathways, Risk Factors
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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