Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 22, Issue 40, Pages 6087-6106Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612822666160922165706
Keywords
Microbiome; gut; probiotics; type 2 diabetes mellitus; obesity; metabolic syndrome; major depressive disorder; psychiatry
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Funding
- European Union [613979]
- Spanish Ministry of Economy and Competitiveness (MINECO, Spain) [AGL2014-52101-P]
- NHMRC [1059660]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq
- Brazil)
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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.
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