Journal
BIOLOGICAL PSYCHIATRY
Volume 80, Issue 11, Pages 849-858Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2015.12.003
Keywords
Chidren; Default mode network; Depression; Familial risk; Resting-state fMRI; Subgenual ACC
Categories
Funding
- Tommy Fuss Fund
- Poitras Center for Affective Disorders Research
- Massachusetts General Hospital Pediatric Psychopharmacology Council Fund
- National Institutes of Health (NIH) [R01 HD036317, R01MH050657, R01 MH636833, R01 MH/CHD076923, R01 MH47077]
- The 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
- Ingenix
- Prophase
- Shire
- Bracket Global
- Theravance
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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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