Interplay Between Frontolimbic Resting State Connectivity And Hypothalamic-Pituitary-Adrenal Axis Functioning In Adolescents With And Without Depression

Abstract

Depression is associated with abnormalities in HPA-axis functioning and neural circuitry that underlie the stress response. Although positive associations have been found between cortisol levels and amygdala metabolism, activation, and volume, the associations between cortisol and resting state functional connectivity (RSFC) has not been examined. RSFC captures intrinsic connections between brain regions that may set the stage for the rallying of the HPA system. The association between frontolimbic RSFC in particular and HPA axis functioning is critical since stress system functioning involves activating to and recovering from threat, processes mediated by limbic and prefrontal activity respectively. The purpose of this study was to examine the association between cortisol and frontolimbic RSFC in healthy controls and adolescents with depression. Overall, healthy controls tended to show positive correlations between frontolimbic connectivity and cortisol levels in the context of the TSST whereas patients with depression showed an inverse relationship. Positive association between neural and HPA stress systems in healthy controls may suggest coordinated upregulation and downregulation of these two stress systems in response to stress. In contrast, in patients with depression, excessive recruitment of the mPFC by the amygdala may interfere with HPA system recruitment efficiency and successful rallying of HPA axis in response to social stress. These findings provide evidence that the intrinsic quality of this frontolimbic channel is related to HPA axis functioning, and patients with MDD show different patterns of associations compared to HC, which may interfere with adaptive stress functioning.