Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression

Background: The incidence of major depressive disorder (MDD) rises during adolescence, yet the neura mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdals RSFC is associated with changes in depressive symptom severity in adolescents. Method: We examined group differences in amygdala RSFC between medication-na ve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset o: the MDD group (N=24). Results: Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressec group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. Limitations: Only a subset of depressed participants was assessed at follow-up and treatment type and deliver, were not standardized. Conclusions: Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insular subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.