Vitamin D and Inflammation in Major Depressive Disorder

Overview

Journal J Affect Disord

Date 2020 Feb 18

PMID 32063570

Citations 14

Authors

Cecile Grudet

Owen M Wolkowitz

Synthia H Mellon

Johan Malm

Victor I Reus

Lena Brundin

Brenton M Nier

Firdaus S Dhabhar

Christina M Hough

Asa Westrin

Daniel Lindqvist

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Peripheral blood cellular immunophenotype in suicidal ideation, suicide attempt, and suicide: a systematic review and meta-analysis.

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Mohammadi Y, Ansari N, Daneshi Maskooni M, Amiri M Iran J Psychiatry. 2023; 18(4):484-492.

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References

Zhang Y, Leung D, Richers B, Liu Y, Remigio L, Riches D . Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012; 188(5):2127-35. PMC: 3368346. DOI: 10.4049/jimmunol.1102412. View

Brundin L, Erhardt S, Bryleva E, Achtyes E, Postolache T . The role of inflammation in suicidal behaviour. Acta Psychiatr Scand. 2015; 132(3):192-203. PMC: 4531386. DOI: 10.1111/acps.12458. View

Schiepers O, Wichers M, Maes M . Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(2):201-17. DOI: 10.1016/j.pnpbp.2004.11.003. View

Anglin R, Samaan Z, Walter S, McDonald S . Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013; 202:100-7. DOI: 10.1192/bjp.bp.111.106666. View

Kjaergaard M, Waterloo K, Wang C, Almas B, Figenschau Y, Hutchinson M . Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry. 2012; 201(5):360-8. DOI: 10.1192/bjp.bp.111.104349. View

Tonelli L, Stiller J, Rujescu D, Giegling I, Schneider B, Maurer K . Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatr Scand. 2007; 117(3):198-206. PMC: 2612100. DOI: 10.1111/j.1600-0447.2007.01128.x. View

Dipietro L, Caspersen C, OSTFELD A, Nadel E . A survey for assessing physical activity among older adults. Med Sci Sports Exerc. 1993; 25(5):628-42. View

Dhabhar F, Burke H, Epel E, Mellon S, Rosser R, Reus V . Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression. J Psychiatr Res. 2009; 43(11):962-9. DOI: 10.1016/j.jpsychires.2009.05.010. View

Kim Y, Lee S, Kim S, Shim S, Han S, Choi S . Differences in cytokines between non-suicidal patients and suicidal patients in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 32(2):356-61. DOI: 10.1016/j.pnpbp.2007.08.041. View

10.

Forget P, Khalifa C, Defour J, Latinne D, Van Pel M, De Kock M . What is the normal value of the neutrophil-to-lymphocyte ratio?. BMC Res Notes. 2017; 10(1):12. PMC: 5217256. DOI: 10.1186/s13104-016-2335-5. View

11.

Holmes S, Hinz R, Conen S, Gregory C, Matthews J, Anton-Rodriguez J . Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biol Psychiatry. 2017; 83(1):61-69. DOI: 10.1016/j.biopsych.2017.08.005. View

12.

Tariq M, Streeten E, Smith H, Sleemi A, Khabazghazvini B, Vaswani D . Vitamin D: a potential role in reducing suicide risk?. Int J Adolesc Med Health. 2011; 23(3):157-65. DOI: 10.1515/ijamh.2011.038. View

13.

Skrobot A, Demkow U, Wachowska M . Immunomodulatory Role of Vitamin D: A Review. Adv Exp Med Biol. 2018; 1108:13-23. DOI: 10.1007/5584_2018_246. View

14.

Dana-Alamdari L, Kheirouri S, Noorazar S . Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder. Iran J Public Health. 2015; 44(5):690-7. PMC: 4537627. View

15.

Howren M, Lamkin D, Suls J . Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009; 71(2):171-86. DOI: 10.1097/PSY.0b013e3181907c1b. View

16.

Wielders J, Wijnberg F . Preanalytical stability of 25(OH)-vitamin D3 in human blood or serum at room temperature: solid as a rock. Clin Chem. 2009; 55(8):1584-5. DOI: 10.1373/clinchem.2008.117366. View

17.

Lindqvist D, Dhabhar F, James S, Hough C, Jain F, Bersani F . Oxidative stress, inflammation and treatment response in major depression. Psychoneuroendocrinology. 2016; 76:197-205. PMC: 5272818. DOI: 10.1016/j.psyneuen.2016.11.031. View

18.

Hanisch U . Microglia as a source and target of cytokines. Glia. 2002; 40(2):140-155. DOI: 10.1002/glia.10161. View

19.

Do J, Kwon S, Park S, Lee E . Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet's disease. Rheumatology (Oxford). 2008; 47(6):840-8. DOI: 10.1093/rheumatology/ken109. View

20.

Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C . Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010; 10(4):482-96. DOI: 10.1016/j.coph.2010.04.001. View