Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression
Open accessAbstract
Background Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression.Methods We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16).Results At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales.Conclusions Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression.
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- Authors
- Chai, X. J., Hirshfeld-Becker, D., Biederman, J., Uchida, M., Doehrmann, O., Leonard, J. A., Salvatore, J., Kenworthy, T., Brown, A., Kagan, E., de los Angeles, C., Gabrieli, J. D. E., & Whitfield-Gabrieli, S.
- Affiliations
- McGovern Institute for Brain Research (US)
- Harvard University (US)
- Corresponding author
- Chai, Xiaoqian J.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 80
- Issue
- 11
- Pages
- 849-858
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4956583
- OpenAlex
- W2204441325
- Cited by
- 75
- References
- 72
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 4
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biological Psychiatry (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Tommy Fuss Fund
- Poitras Center for Affective Disorders Research
- Massachusetts General Hospital Pediatric Psychopharmacology Council Fund
- National Institutes of Health (NIH) (R01 HD036317, R01MH050657)
- NIH (R01 MH636833, R01 MH/CHD076923, R01 MH47077)
- Department of Defense
- American Academy of Child and Adolescent Psychiatry
- Alcobra
- Forest Research Institute
- Ironshore
- Lundbeck
- Magceutics Inc.
- Merck
- PamLab
- Pfizer
- Shire Pharmaceuticals Inc.
- SPRITES
- Sunovion
- Vaya Pharma/Enzymotec
- National Institutes of Health
- MGH
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, familial risk, children, resting-state functional connectivity, default mode network, subgenual anterior cingulate cortex, cognitive control network, dorsolateral prefrontal cortex, amygdala, inferior frontal gyrus, early intervention, neuroimaging biomarkers
- MeSH terms
- Adolescent, Cerebral Cortex, Child, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Risk, Child of Impaired Parents, Genetic Predisposition to Disease, Connectome
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