Vitamin D and inflammation in major depressive disorder
Open accessAbstract
Background Increased inflammation is reported in Major Depressive Disorder (MDD), which may be more pronounced in suicidal subjects. Vitamin D deficiency may drive this pro-inflammatory state due to vitamin D's anti-inflammatory effects. Methods We quantified plasma 25-hydroxyvitamin D (25(OH)D) and inflammatory markers interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and other inflammatory indices, neutrophil-to-lymphocyte ratio (NLR) and white blood cell count (WBC) in 48 un-medicated MDD subjects (n = 17 with mild-to-moderate suicidal ideation [SI]) and 54 controls. IL-6 and TNF-α were combined into a composite inflammation score. Results There were no significant differences in 25(OH)D levels between MDD and controls (p = 0.24) or between MDD with and without SI (p = 0.61). However, 25(OH)D was negatively correlated with all measured inflammatory markers; these correlations were stronger in MDD subjects, and particularly in those with SI. MDD status significantly moderated the relationships between 25(OH)D and NLR (p = 0.03), and 25(OH)D and WBC (p < 0.05), and SI significantly moderated the relationship between 25(OH)D and NLR (p = 0.03). Limitations The study was cross-sectional, thereby limiting causal inference, and had a small sample size. Only seventeen of the MDD subjects had SI. Conclusion While 25(OH)D levels did not significantly differ in MDD vs. controls, or in MDD with or without SI, lower 25(OH)D was associated with indices of immune activation in MDD, especially in cases with SI. Although our findings do not address causality, they are consistent with findings that relatively low 25(OH)D levels in MDD are associated with a pro-inflammatory state.
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In Grudet et al., lower levels of vitamin D were more associated with a pro-inflammatory status in major depressive disorder patients than healthy controls, especially in major depressive disorder patients with suicidal ideation.
“Lower levels of vitamin D were more associated with a pro-inflammatory status in MDD patients than HC, especially in MDD patients with SI”
In Grudet et al., NLR did not show differences between major depressive disorder and healthy controls or between major depressive disorder with suicidal ideation and without suicidal ideation.
“NLR did not show differences between MDD vs HC or between MDD with SI vs without SI”
One study examining the association between current SI and NLR in patients with MDD found no differences between patients with and without current SI in NLR.
“One study examining the association between current SI and NLR in patients with MDD found no differences between patients with and without current SI in NLR [28] (Table 2).”
Three other studies reported no statistically significant differences in NLR between depressed patients with a history of SA and HC.
“However, three other studies reported no statistically significant differences [28, 29, 31] (Table 3).”
The relationship between the increase in NLR and suicidality occurs only in SA and not in SI.
“and it seems that the relationship between the increase in NLR and suicidality occurs only in SA and not in SI [28].”
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Cites
The role of inflammation in depression: from evolutionary imperative to modern treatment target
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Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766 · see citing works
Microglia as a source and target of cytokines
Hanisch, U. (2002) · Glia · doi:10.1002/glia.10161 · Cited by 1,645 · see citing works
Cytokines and major depression
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Role of Inflammation in Suicide: From Mechanisms to Treatment
Brundin, L., Bryleva, E. Y., & Thirtamara Rajamani, K. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.116 · Cited by 257 · see citing works
Self-citationGowda, U., Mutowo, M. P., Smith, B. J., Wluka, A. E., & Renzaho, A. M. N. (2015) · Nutrition · doi:10.1016/j.nut.2014.06.017 · Cited by 229 · see citing works
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Cheng, Y., Wang, Y., Wang, X., Jiang, Z., Zhu, L., & Fang, S. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.893097 · Cited by 110 · see citing works
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- Authors
- Grudet, C., Wolkowitz, O. M., Mellon, S. H., Malm, J., Reus, V. I., Brundin, L., Nier, B. M., Dhabhar, F. S., Hough, C. M., Westrin, Å., & Lindqvist, D.
- Affiliations
- Lund University (SE)
- University of California, San Francisco (US)
- Van Andel Institute (US)
- University of Miami (US)
- University of California, Los Angeles (US)
- Corresponding author
- Lindqvist, Daniel
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 267
- Pages
- 33-41
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC10662683
- OpenAlex
- W3003811366
- Cited by
- 45
- References
- 6
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 5 · 2023: 10 · 2022: 6 · 2021: 5 · 2020: 2
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 317 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Affective Disorders (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- vitamin D, 25-hydroxyvitamin D, major depressive disorder, inflammation, suicidal ideation, interleukin-6, TNF-α, neutrophil-to-lymphocyte ratio, white blood cell count, immune activation
- MeSH terms
- Cross-Sectional Studies, Major Depressive Disorder, Humans, Inflammation, Vitamin D, Vitamins
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