Disrupted intrinsic functional connectivity of the cognitive control network underlies disease severity and executive dysfunction in first-episode, treatment-naive adolescent depression

Previous neuroimaging studies have showed that imbalanced functional integration of distributed large-scale brain networks is associated with pathophysiological characteristics of major depressive disorder (MDD). However, the association between network integrative disturbances and clinical features and cognitive functions remains largely unclear in adolescent MDD. This study investigated the neural correlates of abnormal functional connectivity networks with clinical and cognitive characteristics in adolescent MDD. Twenty-eight first-episode, treatment-naive adolescents with MDD and 24 well-matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) and a battery of cognitive tests. A seed-based functional connectivity (FC) approach was used to depict connectivity patterns of the cognitive control network (CCN), affective network (AN) and default mode network (DMN), whose between-group differences were correlated with clinical variables and cognitive functions in the patients. Compared with the HCs, the MDD patients exhibited impaired executive functions. The FC analysis revealed lower CCN FC with the temporal, parietal and frontal regions and the limbic system, higher AN FC with the temporal and occipital regions and the cerebellum, and lower DMN FC with the cerebellum and insula. Interestingly, the decreased CCN FC was related to disease severity (with the inferior frontal gyrus) and executive dysfunctions (with the middle cingulate gyrus and supramarginal gyrus) in the patients. The main limitations were the relatively small sample size and suboptimal imaging parameters. Functional alteration of CCN during the developmentally sensitive period may be important in the neurobiology of adolescent MDD.