Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

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• 作者：Xiaoqian J. Chai^a ; ^{xiaoqian@mit.edu" class="auth_mail" title="E-mail the corresponding author} ; Dina Hirshfeld-Becker^b ; Joseph Biederman^b ; ^c ; Mai Uchida^b ; ^c ; Oliver Doehrmann^a ; Julia A. Leonard^a ; John Salvatore^a ; Tara Kenworthy^b ; ^c ; Ariel Brown^b ; ^c ; Elana Kagan^b ; ^c ; Carlo de los Angeles^a ; John D.E. Gabrieli^a ; ^b ; ^c ; ^d ; Susan Whitfield-Gabrieli^a
• 关键词：Chidren ; Default mode network ; Depression ; Familial risk ; Resting-state fMRI ; Subgenual ACC
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：80
• 期：11
• 页码：849-858
• 全文大小：1790 K

文摘

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.