Figure 2.

The hypothesis of dysregulation of HPA axis in the pathogenesis of depression. Chronic stress is perceived by the cerebral cortex and amygdala, and transmitted to the hypothalamus (indicated by dashed arrows). Activated PVN releases CRH and AVP into the hypothalamo-hypophyseal portal system. Corticotrophin-releasing hormone and AVP stimulate the corticotropes of the anterior pituitary gland to secrete ACTH into the bloodstream, acting on the zona fasciculata of the adrenal cortex to secrete glucocorticoids. Arrows with plus sign indicate a positive feedback mechanism towards the synthesis and secretion of glucocorticoids into the bloodstream in response to chronic stress. Dotted lines indicate the reduced expression of GR in the prefrontal cortex, hippocampus, PVN, and anterior pituitary gland due to GR-mediated negative feedback loss. The schematic diagram was adapted and modified from Lew et al. (11)