The comorbid prevalence of major depressive disorder (MDD) with obesity and
type II diabetes mellitus reflects the existence of a subset of individuals with a complex
common pathophysiology and overlapping risk factors. Such comorbid disease presentations
imply a number of difficulties, including: decreased treatment responsivity and adherence;
altered glycemic control and increased risk of wider medical complications. A number
of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk
factors such as poor diet and physical inactivity and biological elements including increased
inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction.
All of these biological factors have been extensively investigated in the pathophysiology
of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim
to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus;
(2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity,
and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation,
in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which
the gut-brain axis could play a pivotal role in the comorbidity of these disorders.
Keywords: Microbiome, gut, probiotics, type 2 diabetes mellitus, obesity, metabolic syndrome, major depressive disorder, psychiatry.
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