A review on linking stress, depression, and insulin resistance via low-grade chronic inflammation

Stress is a disturbance in homeostasis caused by psychological, physiological, or environmental factors. Prolonged reactions to chronic stress can be detrimental, resulting in various metabolic abnormalities, referred to as metabolic syndrome (MS). There is a reciprocal increased risk between MS and major depressive disorder. Recent studies established an association between inflammation and insulin signaling in type 2 diabetes mellitus with depression. In the present review, we discuss chronic low-grade inflammation, pathways of insulin resistance, and brain glucose metabolism in the context of neuroinflammation and depression. Specific attention is given to psychotropic drugs such as bupropion, mirtazapine, and nefazodone, anti-inflammatory drugs like Celecoxib (COX-2 inhibitor), Etanercept, adalimumab, IL-4Ra antagonist, Anti-IL- 17A antibody (Ixekizumab) and lifestyle modifications including exercise, dietary changes, and sleep hygiene. These therapeutic solutions offer potential in treating depression by targeting metabolic conditions like insulin resistance and inflammatory pathways. The article further explains the significance of a nutrition and antioxidants-rich diet, emphasizing the role of omega-3 fatty acids, vitamin D, zinc, and polyphenols, to improve immunity and activate anti-inflammatory signaling pathways.