The Role of the Adrenal–Gut–Brain Axis on Comorbid Depressive Disorder Development in Diabetes

Abstract

Diabetic patients are more affected by depression than non-diabetics, and this is related to greater treatment resistance and associated with poorer outcomes. This increase in the prevalence of depression in diabetics is also related to hyperglycemia and hypercortisolism. In diabetics, the hyperactivity of the HPA axis occurs in parallel to gut dysbiosis, weakness of the intestinal permeability barrier, and high bacterial-product translocation into the bloodstream. Diabetes also induces an increase in the permeability of the blood–brain barrier (BBB) and Toll-like receptor 4 (TLR4) expression in the hippocampus. Furthermore, lipopolysaccharide (LPS)-induced depression behaviors and neuroinflammation are exacerbated in diabetic mice. In this context, we propose here that hypercortisolism, in association with gut dysbiosis, leads to an exacerbation of hippocampal neuroinflammation, glutamatergic transmission, and neuronal apoptosis, leading to the development and aggravation of depression and to resistance to treatment of this mood disorder in diabetic patients.

Physiological Correlates of Hypnotizability: Hypnotic Behaviour and Prognostic Role in Medicine

“…Finally, the highs' ability to modulate their autonomic activity [83,90,91], challenged by only one study [92] could positively influence their microbiota, whose alteration is involved in cognitive decline owing to the cerebral effects of locally produced cytokines and the activation of afferent vagal fibers [93]. The negative effects of microbiota alteration of have been described, in fact, in case of degenerative physical and cognitive decline [94][95][96][97][98][99][100].…”