Aberrant Resting-state Functional Connectivity in Limbic and Salience Networks in Treatment--naïve Clinically Depressed Adolescents

Background: Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network.

Methods: Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network).

Results: Compared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures.

Conclusions: The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.