Neuroendocrine cortisol pathway genes and the comorbidity of depression, T2D, and metabolic syndrome

What is it about?

Type 2 diabetes (T2D) is associated with an increased for major depressive disorder, and conversely, depression increases T2D risk, an association not attributed to antidepressant therapy. T2D also is associated with metabolic syndrome. All three conditions are associated with high cortisol levels. This review focuses on the correlation of stress, hypothalamic-pituitary-adrenal (HPA) hyperactivation, and the possible genetic role of the CRH receptors (CRHR1, CRHR2), corticotropin receptors (or melanocortin receptors, MC1R-MC5R), glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), and the FK506 binding protein 51 (FKBP5) in susceptibility to the comorbidity of depression, T2D and metabolic syndrome.

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Why is it important?

Based on the evidence, the authors hypothesize that variants in the CRHR1, CRHR2, MC1R-MC5R, NR3C1, NR3C2, and FKBP5 genes may hyperactivate the HPA axis and be partially responsible for the clinical association of depression, T2D, and metabolic syndrome. It calls for studies to confirm the hypothesis.