Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients
Abstract
There is evidence that there is a bidirectional relationship between major depression and cardiovascular disorder (CVD): depressed patients are a population at risk for increased cardiac morbidity and mortality, and depression is more frequent in patients who suffer from CVD. There is also evidence that inflammatory and oxidative and nitrosative stress (IO&NS) pathways underpin the common pathophysiology of both CVD and major depression. Activation of these pathways may increase risk for both disorders and contribute to shared risk. The shared IO&NS pathways that may contribute to CVD and depression comprise the following: increased levels of pro-inflammatory cytokines, like interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-γ; T cell activation; increased acute phase proteins, like C-reactive protein, haptoglobin, fibrinogen and α1-antitrypsin; complement factors; increased LPS load through bacterial translocation and subsequent gut-derived inflammation; induction of indoleamine 2,3-dioxygenase with increased levels of tryptophan catabolites; decreased levels of antioxidants, like coenzyme Q10, zinc, vitamin E, glutathione and glutathione peroxidase; increased O&NS characterized by oxidative damage to low density lipoprotein (LDL) and phospholipid inositol, increased malondialdehyde, and damage to DNA and mitochondria; increased nitrosative stress; and decreased ω3 polyunsaturated fatty acids (PUFAs). The complex interplay between the abovementioned IO&NS pathways in depression results in pro-atherogenic effects and should be regarded as a risk factor to future clinical CVD and due mortality. We suggest that major depression should be added as a risk factor to the Charlson "comorbidity" index. It is advised that patients with (sub)chronic or recurrent major depression should routinely be assessed by serology tests to predict if they have an increased risk to cardiovascular disorders.
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Oxidative (and nitrosative) stress may cause neurodegeneration and reduced neurogenesis.
“Considering that the presence of oxidative (and nitrosative) stress may cause neurodegeneration and reduced neurogenesis [63, 64]”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [63]
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- Authors
- Maes, M., Ruckoanich, P., Chang, Y. S., Mahanonda, N., & Berk, M.
- Affiliations
- Piyavate Hospital (TH)
- Mental Health Research Institute (AU)
- Corresponding author
- Maes, Michael
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 35
- Issue
- 3
- Pages
- 769-783
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2011854518
- Cited by
- 169
- References
- 288
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 10 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 13 · 2015: 15 · 2014: 12 · 2013: 12 · 2012: 12
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- major depressive disorder, cardiovascular disease, inflammatory signaling, oxidative stress, nitrosative stress, inflammatory cytokines, acute phase proteins, complement system, lipopolysaccharide, tryptophan catabolites, indoleamine 2,3-dioxygenase, antioxidants, atherosclerosis, omega-3 polyunsaturated fatty acids, cardiovascular mortality, Charlson Comorbidity Index
- MeSH terms
- Animals, Antioxidants, Cardiovascular Diseases, Depression, Female, Humans, Inflammation, Male, Risk, Fatty Acids, Omega-3, Nitrosation, Comorbidity, Oxidative Stress
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