Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment
-
Laya Kafami
,
Sara Assadiasl
,
Sara Hashempour
,
Mohammad Hossein Niknam
,
Bahareh Mohebbi
,
Mohammad Amin Hashemnezhad
,
Bita Ansaripour
,
Arash Mirabzadeh
,
Banafsheh Mosharmovahed
,
Fateme Fazli
,
Mahshid Saleh
,
Nam i Mohammadian Khanssari
,
Ahmad Ali Noorbala
Abstract
Depression is one of the current dilemmas in both developed and developing societies. Studies show that the severity of psychiatric symptoms is directly related to the degree of inflammation caused by cytokines secreted by the immune system. Hence, evaluating serum cytokine levels in patients with depression can help to understand the pathogenesis of the disease and make the best therapeutic decisions. The present study investigated the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients with major depression or bipolar disorder during depressive episodes (BDDE) before and after a 6-month pharmaceutical intervention.
Patients referring to 3 clinics were recruited for the study. The diagnosis of major depression or bipolar disorder in a depressive phase was made according to the Diagnostic and Statistical Manual of Mental Disorders -5(DSM-5) criteria.
There was a significant difference in depression levels between the pre-intervention and 6-month follow-up in both groups. After 6 months, IL-1 and IL-6 levels in the bipolar disorder group had decreased while TNF-α levels had increased. There was also a significant difference between pre-intervention and follow-up levels of IL-1.
Serum levels of IL-1 and IL-6 decreased significantly in both groups after the 6-month follow-up, and symptom improvement was observed. TNF-α levels, on the other hand, decreased in the major depression group but increased in the bipolar disorder group.
Considering that inflammation is a major outcome of depression, treatment strategies to reduce inflammation could be a practical approach to improving psychiatric symptoms.
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5. Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep. 2018;8(1):1-10.
6. Teixeira AL, Colpo GD, Fries GR, Bauer IE, Selvaraj S. Biomarkers for bipolar disorder: current status and challenges ahead. Expert Rev Neurother. 2019;19(1):67-81.
7. Haapakoski R, Ebmeier KP, Alenius H, Kivimäki M. Innate and adaptive immunity in the development of depression: an update on current knowledge and technological advances. Prog. Neuro-Psychopharmacol Biol Psychiatry. 2016;66:63-72.
8. Sayana P, Colpo GD, Simoes LR, Giridharan VV, Teixeira AL, Quevedo J, et al. A systematic review of evidence for the role of inflammatory biomarkers in bipolar patients. J Psychiatr Res. 2017;92(9):160-82.
9. Höglund E, Øverli Ø, Winberg S. Tryptophan metabolic pathways and brain serotonergic activity: a comparative review. Front endocrinol. 2019;10(4):158.
10. Cox D, Chan MK, Bahn S. The potential of immune biomarkers to advance personalized medicine approaches for schizophrenia. J Nerv Ment Dis. 2015;203(5):393-9.
11. Tasic L, Larcerda AL, Pontes JG, da Costa TB, Nani JV, Martins LG, et al. Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder. J Psychiatr Res. 2019;119(24):67-75.
12. Becking K, Haarman BC, Grosse L, Nolen WA, Claes S, Arolt V, et al. The circulating levels of CD4+ t helper cells are higher in bipolar disorder as compared to major depressive disorder. J Neuroimmunol. 2018;319(18):28-36.
13. Brietzke E, Stertz L, Fernandes BS, Kauer-Sant’Anna M, Mascarenhas M, Vargas AE, et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116(3):214-7.
14. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A Meta-Analysis of Cytokines in Major Depression. Biol Psychiatry. 2010;67(5):446-57.
15. Benedetti F, Poletti S, Hoogenboezem TA, Locatelli C, de Wit H, Wijkhuijs AJ, et al. Higher baseline pro-inflammatory cytokines mark poor antidepressant response in bipolar disorder. J Clin Psychiatry. 2017;78(8):986-93.
16. Farooq RK, Asghar K, Kanwal S, Zulqernain A. Role of inflammatory cytokines in depression: Focus on interleukin-1β. Biomed Reports. 2017;6(1):15-20.
17. Hayley S. Toward an anti-inflammatory strategy for depression. Front Behav Neurosci. 2011;5:19.
18. Jazayeri S, Keshavarz SA, Tehrani-Doost M, Djalali M, Hosseini M, Amini H, et al. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Res. 2010;178(1):112-5.
19. Miller ES, Sakowicz A, Roy A, Yang A, Sullivan JT, Grobman WA, et al. Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression. Am J Obstet Gynecol. 2019;220(3):271.
20. Brietzke E, Kapczinski F. TNF-α as a molecular target in bipolar disorder. Prog Neuro-Psychopharmacol. Biol Psychiatry. 2008;32(6):1355-61.
21. Gupta R, Gupta K, Tripathi A, Bhatia M, Gupta LK. Effect of mirtazapine treatment on serum levels of brain-derived neurotrophic factor and tumor necrosis factor-α in patients of major depressive disorder with severe depression. Pharmacol. 2016;97(3-4):184-8.
22. Leonard BE. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr. 2018;30(1):1-16.
23. Zellweger MJ, Osterwalder RH, Langewitz W, Pfisterer ME. Coronary artery disease and depression. Eur Heart J. 2004;25(1):3-9.
24. Margaretten M, Julian L, Katz P, Yelin E. Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumatol. 2011;6(6):617.
25. Kim Y-K, Na K-S, Shin K-H, Jung H-Y, Choi S-H, Kim J-B. Cytokine imbalance in the pathophysiology of major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007;31(5):1044-53.
26. Na K-S, Chang HS, Won E, Han K-M, Choi S, Tae WS, et al. Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PloS one. 2014;9(1):e85425.
27. Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord. 2002;72(3):237-41.
28. Shabani A, Akbari M, Dadashi M. Reliability and validity of the Bipolar Depression Rating Scale on an Iranian sample. Arch Iran Med. 2010; 13(3):217-22.
29. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacol. 2011;36(12):2452-9.
30. Haroon E, Daguanno AW, Woolwine BJ, Goldsmith DR, Baer WM, Wommack EC, et al. Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinol. 2018;95(14):43-9.
31. Wang L, Wang R, Liu L, Qiao D, Baldwin DS, Hou R. Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis. Brain Behav Immun. 2019;79(14):24-38.
32. Munkholm K, Braüner JV, Kessing LV, Vinberg M. Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res. 2013;47(9):1119-33.
33. Eyre HA, Air T, Pradhan A, Johnston J, Lavretsky H, Stuart MJ, et al. A meta-analysis of chemokines in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;68(14):1-8.
34. van den Ameele S, van Diermen L, Staels W, Coppens V, Dumont G, Sabbe B, et al. The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: a systematic review. J Affect Disord. 2016;203(25):364-73.
35. Ortiz‐Domínguez A, Hernández ME, Berlanga C, Gutiérrez‐Mora D, Moreno J, Heinze G, et al. Immune variations in bipolar disorder: phasic differences. Bipolar Disord. 2007;9(6):596-602.
36. Knijff EM, Nadine Breunis M, Kupka RW, De Wit HJ, Ruwhof C, Akkerhuis GW, et al. An imbalance in the production of IL‐1β and IL‐6 by monocytes of bipolar patients: restoration by lithium treatment. Bipolar Disord. 2007;9(7):743-53.
37. Remlinger-Molenda A, Wojciak P, Michalak M, Karczewski J, Rybakowski JK. Selected cytokine profiles during remission in bipolar patients. Neuropsychobiol. 2012;66(3):193-8.
38. Valvassori SS, Tonin PT, Varela RB, Carvalho AF, Mariot E, Amboni RT, et al. Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine. Bipolar Disord. 2015;17(5):507-17.
39. Uyanik V, Tuglu C, Gorgulu Y, Kunduracilar H, Uyanik MS. Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment. Psychiatr Res. 2015;228(3):386-92.
40. Goldsmith D, Rapaport M, Miller B. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696-709.
2. Sadeghirad B, Haghdoost A-A, Amin-Esmaeili M, Ananloo ES, Ghaeli P, Rahimi-Movaghar A, et al. Epidemiology of major depressive disorder in Iran: a systematic review and meta-analysis. Int J Prev Med. 2010;1(2):81-9.
3. Sagar R, Pattanayak RD. Potential biomarkers for bipolar disorder: Where do we stand? Ind J Med Res. 2017;145(1):7-9.
4. Bueno-Notivol J, Gracia-García P, Olaya B, Lasheras I, López-Antón R, Santabárbara J. Prevalence of depression during the COVID-19 outbreak: A meta-analysis of community-based studies. Int J Clin Health Psychol. 2021;21(1):100196.
5. Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep. 2018;8(1):1-10.
6. Teixeira AL, Colpo GD, Fries GR, Bauer IE, Selvaraj S. Biomarkers for bipolar disorder: current status and challenges ahead. Expert Rev Neurother. 2019;19(1):67-81.
7. Haapakoski R, Ebmeier KP, Alenius H, Kivimäki M. Innate and adaptive immunity in the development of depression: an update on current knowledge and technological advances. Prog. Neuro-Psychopharmacol Biol Psychiatry. 2016;66:63-72.
8. Sayana P, Colpo GD, Simoes LR, Giridharan VV, Teixeira AL, Quevedo J, et al. A systematic review of evidence for the role of inflammatory biomarkers in bipolar patients. J Psychiatr Res. 2017;92(9):160-82.
9. Höglund E, Øverli Ø, Winberg S. Tryptophan metabolic pathways and brain serotonergic activity: a comparative review. Front endocrinol. 2019;10(4):158.
10. Cox D, Chan MK, Bahn S. The potential of immune biomarkers to advance personalized medicine approaches for schizophrenia. J Nerv Ment Dis. 2015;203(5):393-9.
11. Tasic L, Larcerda AL, Pontes JG, da Costa TB, Nani JV, Martins LG, et al. Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder. J Psychiatr Res. 2019;119(24):67-75.
12. Becking K, Haarman BC, Grosse L, Nolen WA, Claes S, Arolt V, et al. The circulating levels of CD4+ t helper cells are higher in bipolar disorder as compared to major depressive disorder. J Neuroimmunol. 2018;319(18):28-36.
13. Brietzke E, Stertz L, Fernandes BS, Kauer-Sant’Anna M, Mascarenhas M, Vargas AE, et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116(3):214-7.
14. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A Meta-Analysis of Cytokines in Major Depression. Biol Psychiatry. 2010;67(5):446-57.
15. Benedetti F, Poletti S, Hoogenboezem TA, Locatelli C, de Wit H, Wijkhuijs AJ, et al. Higher baseline pro-inflammatory cytokines mark poor antidepressant response in bipolar disorder. J Clin Psychiatry. 2017;78(8):986-93.
16. Farooq RK, Asghar K, Kanwal S, Zulqernain A. Role of inflammatory cytokines in depression: Focus on interleukin-1β. Biomed Reports. 2017;6(1):15-20.
17. Hayley S. Toward an anti-inflammatory strategy for depression. Front Behav Neurosci. 2011;5:19.
18. Jazayeri S, Keshavarz SA, Tehrani-Doost M, Djalali M, Hosseini M, Amini H, et al. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Res. 2010;178(1):112-5.
19. Miller ES, Sakowicz A, Roy A, Yang A, Sullivan JT, Grobman WA, et al. Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression. Am J Obstet Gynecol. 2019;220(3):271.
20. Brietzke E, Kapczinski F. TNF-α as a molecular target in bipolar disorder. Prog Neuro-Psychopharmacol. Biol Psychiatry. 2008;32(6):1355-61.
21. Gupta R, Gupta K, Tripathi A, Bhatia M, Gupta LK. Effect of mirtazapine treatment on serum levels of brain-derived neurotrophic factor and tumor necrosis factor-α in patients of major depressive disorder with severe depression. Pharmacol. 2016;97(3-4):184-8.
22. Leonard BE. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr. 2018;30(1):1-16.
23. Zellweger MJ, Osterwalder RH, Langewitz W, Pfisterer ME. Coronary artery disease and depression. Eur Heart J. 2004;25(1):3-9.
24. Margaretten M, Julian L, Katz P, Yelin E. Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumatol. 2011;6(6):617.
25. Kim Y-K, Na K-S, Shin K-H, Jung H-Y, Choi S-H, Kim J-B. Cytokine imbalance in the pathophysiology of major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007;31(5):1044-53.
26. Na K-S, Chang HS, Won E, Han K-M, Choi S, Tae WS, et al. Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PloS one. 2014;9(1):e85425.
27. Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord. 2002;72(3):237-41.
28. Shabani A, Akbari M, Dadashi M. Reliability and validity of the Bipolar Depression Rating Scale on an Iranian sample. Arch Iran Med. 2010; 13(3):217-22.
29. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacol. 2011;36(12):2452-9.
30. Haroon E, Daguanno AW, Woolwine BJ, Goldsmith DR, Baer WM, Wommack EC, et al. Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinol. 2018;95(14):43-9.
31. Wang L, Wang R, Liu L, Qiao D, Baldwin DS, Hou R. Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis. Brain Behav Immun. 2019;79(14):24-38.
32. Munkholm K, Braüner JV, Kessing LV, Vinberg M. Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res. 2013;47(9):1119-33.
33. Eyre HA, Air T, Pradhan A, Johnston J, Lavretsky H, Stuart MJ, et al. A meta-analysis of chemokines in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;68(14):1-8.
34. van den Ameele S, van Diermen L, Staels W, Coppens V, Dumont G, Sabbe B, et al. The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: a systematic review. J Affect Disord. 2016;203(25):364-73.
35. Ortiz‐Domínguez A, Hernández ME, Berlanga C, Gutiérrez‐Mora D, Moreno J, Heinze G, et al. Immune variations in bipolar disorder: phasic differences. Bipolar Disord. 2007;9(6):596-602.
36. Knijff EM, Nadine Breunis M, Kupka RW, De Wit HJ, Ruwhof C, Akkerhuis GW, et al. An imbalance in the production of IL‐1β and IL‐6 by monocytes of bipolar patients: restoration by lithium treatment. Bipolar Disord. 2007;9(7):743-53.
37. Remlinger-Molenda A, Wojciak P, Michalak M, Karczewski J, Rybakowski JK. Selected cytokine profiles during remission in bipolar patients. Neuropsychobiol. 2012;66(3):193-8.
38. Valvassori SS, Tonin PT, Varela RB, Carvalho AF, Mariot E, Amboni RT, et al. Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine. Bipolar Disord. 2015;17(5):507-17.
39. Uyanik V, Tuglu C, Gorgulu Y, Kunduracilar H, Uyanik MS. Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment. Psychiatr Res. 2015;228(3):386-92.
40. Goldsmith D, Rapaport M, Miller B. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696-709.
| Files | ||
| Issue | Vol 22 No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i2.12681 | |
| Keywords | ||
| Bipolar disorder Inflammatory cytokines Interleukin-1 Interleukin-6 Major depressive disorder Tumor necrosis factor-α | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Kafami L, Assadiasl S, Hashempour S, Niknam MH, Mohebbi B, Hashemnezhad MA, Ansaripour B, Mirabzadeh A, Mosharmovahed B, Fazli F, Saleh M, i Mohammadian Khanssari N, Noorbala AA. Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment. Iran J Allergy Asthma Immunol. 2023;22(2):200-207.
