Association between the Blood-Inflammatory Index with De-pression and Anxiety in a Large Population
-
Mina Nosrati
,
Hossein Hatamzadeh
,
Amin Mansoori
,
Mahsa Tousi
,
Shakiba Najjar Khalilabad
,
Fatemeh Rojoee
,
Fatemeh Mohammadyari
,
Gordon A Ferns
,
Habibollah Esmaily
,
Majid Ghayour-Mobarhan
Abstract
Background: Inflammatory indices have been linked to mood disorders. We aimed to examine whether these inflammatory indices are associated with the severity of depression and anxiety as measured by Beck scores.
Methods: This cross-sectional analysis included 9,704 participants aged 35–65 years from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. Depression and anxiety were assessed using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Inflammatory indices were calculated based on hematological and biochemical parameters. Multinomial logistic regression was applied to evaluate the associations between inflammatory markers and mood disorder severity.
Results: In cases of severe depression, the neutrophil-to-lymphocyte ratio (NLR), white blood cell (WBC) count, and serum high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher (OR = 1.29, 1.08, and 1.01, respectively; P < 0.05) than in individuals with minimal depression. Serum hs-CRP levels were also significantly higher (OR = 0.98; 95% CI: 0.95–0.99) in participants with moderate anxiety compared with those with minimal anxiety.
Conclusion: Higher levels of depression were associated with increased inflammatory hematological indices, and that the severity of depression was related to elevated levels of NLR, WBC, and hs-CRP.
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16. Arbel Y, Finkelstein A, Halkin A, et al (2012). Neutrophil/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients undergoing angiography. Atherosclerosis, 225 (2):456-460.
17. Imtiaz F, Shafique K, Mirza SS, et al (2012). Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med, 5 (1):2.
18. Liang M, Du B, Zhang H, et al (2020). NLR is associated with geriatric depression in Chinese women: a community-based cross-sectional study in eastern China. Front Psychol, 10:2941.
19. Kasama T, Miwa Y, Isozaki T, et al (2005). Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy, 4 (3):273-279.
20. Yin J, Gong R, Zhang M, et al (2023). Associations between sleep disturbance, inflammatory markers and depressive symptoms: Mediation analyses in a large NHANES community sample. Prog Neuropsychopharmacol Biol Psychiatry, 126:110786.
21. Ekinci O, Ekinci A (2017). The connections among suicidal behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a specific relationship with the neutrophil-to-lymphocyte ratio. Nord J Psychiatry, 71 (8):574-580.
22. Meng G, Wang L, Wang X, et al (2019). Association between neutrophil to lymphocyte ratio and depressive symptoms among Chinese adults: a population study from the TCLSIH cohort study. Psychoneuroendocrinology, 103:76-82.
23. Shafiee M, Tayefi M, Hassanian SM, et al (2017). Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology, 84:101-108.
24. Raison CL, Capuron L, Miller AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol, 27 (1):24-31.
25. Maes M, Ringel K, Kubera M, et al (2012). Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression. J Affect Disord, 136 (3):386-392.
26. Akira S, Taga T, Kishimoto T (1993). Interleukin-6 in biology and medicine. Adv Immunol, 54:1-78.
27. Tuglu C, Kara S (2003). Depression, cytokines and immune system. Klinik Psikofarmakoloji Bulteni, 13:142-150.
28. Miller GE, Cohen S, Herbert TB (1999). Pathways linking major depression and immunity in ambulatory female patients. Psychosom Med, 61 (6):850-860.
29. Zorrilla EP, Luborsky L, McKay JR, et al (2001). The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun, 15 (3):199-226.
30. Guerrero LR, Hong S, Tarraf W, et al (2023). Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). PLoS One, 18 (8):e0289833.
31. Pitharouli MC, Hagenaars SP, Glanville KP, et al (2021). Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: results from the UK Biobank. Am J Psychiatry, 178 (6):522-529.
32. Tabatabaeizadeh SA, Abdizadeh MF, Meshkat Z, et al (2018). There is an association between serum high-sensitivity C-reactive protein (hs-CRP) concentrations and depression score in adolescent girls. Psychoneuroendocrinology, 88:102-104.
33. Dowlati Y, Herrmann N, Swardfager W, et al (2010). A meta-analysis of cytokines in major depression. Biol Psychiatry, 67 (5):446-457.
2. Guo B, Zhang M, Hao W, et al (2023). Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Transl Psychiatry, 13 (1):5.
3. Malhi GS, Mann JJ (2018). Seminar depression. Lancet, 392(10161):2299-2312.
4. Liu X, Bai X, Ren R, et al (2022). Association between depression or anxiety symptoms and immune-inflammatory characteristics in in-patients with tuberculosis: a cross-sectional study. Front Psychiatry, 13:985823.
5. Köhler-Forsberg O, Buttenschøn HN, Tansey KE, et al (2017). Association between C-reactive protein (CRP) with depression symptom severity and specific depressive symptoms in major depression. Brain Behav Immun, 62:344-350.
6. Su M, Ouyang X, Song Y (2022). Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in depression: A meta-analysis. J Affect Disord, 308:375-383.
7. Milaneschi Y, Kappelmann N, Ye Z, et al (2021). Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Mol Psychiatry, 26 (12):7393-7402.
8. Ghayour-Mobarhan M, Moohebati M, Esmaily H, et al (2015). Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation. Int J Public Health, 60(5):561-572.
9. Mirhafez SR, Zarifian A, Ebrahimi M, et al (2015). Relationship between serum cytokine and growth factor concentrations and coronary artery disease. Clin Biochem, 48 (9):575-580.
10. Mirhafez SR, Pasdar A, Avan A, et al (2015). Cytokine and growth factor profiling in patients with the metabolic syndrome. Br J Nutr, 113 (12):1911-1919.
11. Mardan-Nik M, Pasdar A, Jamialahmadi K, et al (2016). Association of heat shock protein70-2 (HSP70-2) gene polymorphism with obesity. Ann Hum Biol, 43 (6):542-546.
12. Ghassemzadeh H, Mojtabai R, Karamghadiri N, et al (2005). Psychometric properties of a Persian‐language version of the Beck Depression Inventory‐Second edition: BDI‐II‐PERSIAN. Depress Anxiety, 21 (4):185-192.
13. Kaviani H, Mousavi A (2008). Psychometric properties of the Persian version of Beck Anxiety Inventory (BAI). Tehran Univ Med J, 66(2): 136-140.
14. Sunbul EA, Sunbul M, Yanartas O, et al (2016). Increased neutrophil/lymphocyte ratio in patients with depression is correlated with the severity of depression and cardiovascular risk factors. Psychiatry Investig, 13 (1):121-6.
15. Dinan TG (2009). Inflammatory markers in depression. Curr Opin Psychiatry, 22 (1):32-36.
16. Arbel Y, Finkelstein A, Halkin A, et al (2012). Neutrophil/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients undergoing angiography. Atherosclerosis, 225 (2):456-460.
17. Imtiaz F, Shafique K, Mirza SS, et al (2012). Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med, 5 (1):2.
18. Liang M, Du B, Zhang H, et al (2020). NLR is associated with geriatric depression in Chinese women: a community-based cross-sectional study in eastern China. Front Psychol, 10:2941.
19. Kasama T, Miwa Y, Isozaki T, et al (2005). Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy, 4 (3):273-279.
20. Yin J, Gong R, Zhang M, et al (2023). Associations between sleep disturbance, inflammatory markers and depressive symptoms: Mediation analyses in a large NHANES community sample. Prog Neuropsychopharmacol Biol Psychiatry, 126:110786.
21. Ekinci O, Ekinci A (2017). The connections among suicidal behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a specific relationship with the neutrophil-to-lymphocyte ratio. Nord J Psychiatry, 71 (8):574-580.
22. Meng G, Wang L, Wang X, et al (2019). Association between neutrophil to lymphocyte ratio and depressive symptoms among Chinese adults: a population study from the TCLSIH cohort study. Psychoneuroendocrinology, 103:76-82.
23. Shafiee M, Tayefi M, Hassanian SM, et al (2017). Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology, 84:101-108.
24. Raison CL, Capuron L, Miller AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol, 27 (1):24-31.
25. Maes M, Ringel K, Kubera M, et al (2012). Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression. J Affect Disord, 136 (3):386-392.
26. Akira S, Taga T, Kishimoto T (1993). Interleukin-6 in biology and medicine. Adv Immunol, 54:1-78.
27. Tuglu C, Kara S (2003). Depression, cytokines and immune system. Klinik Psikofarmakoloji Bulteni, 13:142-150.
28. Miller GE, Cohen S, Herbert TB (1999). Pathways linking major depression and immunity in ambulatory female patients. Psychosom Med, 61 (6):850-860.
29. Zorrilla EP, Luborsky L, McKay JR, et al (2001). The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun, 15 (3):199-226.
30. Guerrero LR, Hong S, Tarraf W, et al (2023). Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). PLoS One, 18 (8):e0289833.
31. Pitharouli MC, Hagenaars SP, Glanville KP, et al (2021). Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: results from the UK Biobank. Am J Psychiatry, 178 (6):522-529.
32. Tabatabaeizadeh SA, Abdizadeh MF, Meshkat Z, et al (2018). There is an association between serum high-sensitivity C-reactive protein (hs-CRP) concentrations and depression score in adolescent girls. Psychoneuroendocrinology, 88:102-104.
33. Dowlati Y, Herrmann N, Swardfager W, et al (2010). A meta-analysis of cytokines in major depression. Biol Psychiatry, 67 (5):446-457.
| Files | ||
| Issue | Vol 54 No 12 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Depression Anxiety C-Reactive protein Inflammation Blood | ||
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How to Cite
1.
Nosrati M, Hatamzadeh H, Mansoori A, Tousi M, Najjar Khalilabad S, Rojoee F, Mohammadyari F, Ferns GA, Esmaily H, Ghayour-Mobarhan M. Association between the Blood-Inflammatory Index with De-pression and Anxiety in a Large Population. Iran J Public Health. 2025;54(12):2745-2753.
