Central and Peripheral Inflammation Link Metabolic Syndrome and Major Depressive Disorder
Open accessAbstract
Metabolic syndrome and major depression are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. Recent studies have uncovered that each of these conditions is associated with chronic, low-grade inflammation. This is characterized by increased circulating pro-inflammatory cytokines, altered leukocyte population frequencies in blood, accumulation of immune cells in tissues including the brain, and activation of these immune cells. Cytokines that become elevated during obesity can contribute to the progression of metabolic syndrome by directly causing insulin resistance. During chronic stress, there is evidence that these cytokines promote depression-like behavior by disrupting neurotransmitter synthesis and signal transduction. Animal models of obesity and depression have revealed a bi-directional relationship whereby high-fat feeding and chronic stress synergize and exacerbate metabolic dysregulation and behavioral abnormalities. Although far from conclusive, emerging evidence suggests that inflammation in the central and peripheral immune system may link metabolic syndrome to major depressive disorder. In this review, we will synthesize available data supporting this view and identify critical areas for future investigation.
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People with MDD frequently also have immune and inflammatory conditions such as rheumatoid arthritis, cardiovascular disease, metabolic syndrome and IBD.
“Unsurprisingly, people with MDD display high rates of co-morbidity with immune and inflammatory conditions, such as rheumatoid arthritis, cardiovascular disease, metabolic syndrome and inflammatory bowel disease (IBD)9–12.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [11]
The Introduction (page unavailable) identifies cardiovascular disease as an MDD comorbidity and says comorbidity with metabolic syndrome is well recognized, though it varies across cohorts. The passages retrieved from our copy do not establish high rates of MDD comorbidity with rheumatoid arthritis or inflammatory bowel disease, so the full list is not supported by this source. (LLM, conf=0.88)
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Neurobiology of Resilience: Interface Between Mind and Body
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Stress and serum cortisol levels in major depressive disorder: a cross-sectional study
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“Obesity can cause a wide range of changes including increased inflammation in both the periphery and the brain (Ellulu et al., 2017; Chan et al., 2019).”
BackgroundDepression in nonalcoholic fatty liver disease and all-cause/cause-specific mortality
Kim, D., Manikat, R., Shaikh, A., Cholankeril, G., & Ahmed, A. (2024) · European Journal of Clinical Investigation · doi:10.1111/eci.14087 · Cited by 17 · see citing works
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The link between depression, eating behaviors and body mass index
Gasaneo, S., Sánchez, F., Guevara Cruz, R. S., Tabullo, Á. J., Delrieux, C., & Gasaneo, G. (2025) · Psychology, Health & Medicine · doi:10.1080/13548506.2025.2604272
- Authors
- Chan, K. L., Cathomas, F., & Russo, S. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Physiology
- Publisher
- American Physiological Society
- Published
- 2019-03-01
- Volume
- 34
- Issue
- 2
- Pages
- 123-133
- ISSN
- 0886-1714 (ISSN-L)
- 1548-9213
- 1548-9221
- PMC
- PMC6586832
- OpenAlex
- W2913595316
- Cited by
- 227
- References
- 154
- Citations by year
- 2026: 21 · 2025: 39 · 2024: 43 · 2023: 35 · 2022: 31 · 2021: 24 · 2020: 22 · 2019: 12
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (NIMH) (RO1 MH090264, P50 MH096890, RO1 MH104559, P50 AT008661-01)
- Swiss National Science Foundation (Schweizerische Nationalfonds)
- University of Zurich
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- metabolic syndrome, major depressive disorder, low-grade inflammation, inflammatory cytokines, obesity, insulin resistance, chronic stress, high-fat feeding, comorbidities, neurotransmitter synthesis
- MeSH terms
- Animals, Depressive Disorder, Major, Major Depressive Disorder, Encephalitis, Humans, Inflammation, Leukocytes, Obesity, Stress, Psychological, Cytokines, Inflammation Mediators, Metabolic Syndrome
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