TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms

Hongmei Liu, Xiaohui Wu, Yun Wang, Xiaohua Liu, Daihui Peng, Yan Wu, Jun Chen, Yun'ai Su, Jia Xu, Xiancang Ma, Yi Li, Jianfei Shi, Xiaodong Yang, Han Rong, Marta Di Forti, Yiru Fang, Hongmei Liu, Xiaohui Wu, Yun Wang, Xiaohua Liu, Daihui Peng, Yan Wu, Jun Chen, Yun'ai Su, Jia Xu, Xiancang Ma, Yi Li, Jianfei Shi, Xiaodong Yang, Han Rong, Marta Di Forti, Yiru Fang

Abstract

Background: The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD.

Aims: We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.

Methods: The sample consisted of participants (aged 18-55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis.

Results: Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.

Conclusions: This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.

Trial registration number: NCT03219008.

Keywords: antibody array; anxious; atypical; inflammatory markers; major depressive disorder; melancholic; somatic symptoms.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of the study. DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; 17-HDRS, 17-item Hamilton Depression Rating Scale; MDD, major depressive disorder
Figure 2
Figure 2
Peripheral levels of TNF-α, IL-6 and hsCRP in melancholic, atypical and anxious depression and HC participants at baseline. (A) hsCRP; (B) TNF-α; (C) IL-6. The horizontal ordinate represents the three subtypes of MDD and HC participants. The longitudinal coordinates represent the baseline inflammatory marker levels after a log2 transformation detected by an antibody array analysis. The solid and dotted lines on the violin diagram indicated the median and IQR of the measured levels of the inflammatory markers that were logarithmically transformed, respectively. hsCRP, high-sensitivity C reactive protein; HC, healthy control; IL, interleukin; IQR, interquartile range; MDD, major depressive disorder; TNF-α, tumour necrosis factor-α.

References

    1. Park S-C, Kim Y-K. Challenges and strategies for current classifications of depressive disorders: proposal for future diagnostic standards. In: Kim Y-K, ed. Major depressive disorder: rethinking and understanding recent discoveries. Singapore: Springer Singapore, 2021: 103–16.
    1. Simon GE, Perlis RH. Personalized medicine for depression: can we match patients with treatments? Am J Psychiatry 2010;167:1445–55. 10.1176/appi.ajp.2010.09111680
    1. Merikangas KR, Wicki W, Angst J. Heterogeneity of depression. classification of depressive subtypes by longitudinal course. Br J Psychiatry 1994;164:342–8. 10.1192/bjp.164.3.342
    1. Beijers L, Wardenaar KJ, van Loo HM, et al. . Data-driven biological subtypes of depression: systematic review of biological approaches to depression subtyping. Mol Psychiatry 2019;24:888–900. 10.1038/s41380-019-0385-5
    1. van Loo HM, de Jonge P, Romeijn J-W, et al. . Data-driven subtypes of major depressive disorder: a systematic review. BMC Med 2012;10:156. 10.1186/1741-7015-10-156
    1. Fava M, Rush AJ, Alpert JE, et al. . Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008;165:342–51. 10.1176/appi.ajp.2007.06111868
    1. Ionescu DF, Nugent AC, Luckenbaugh DA, et al. . Baseline working memory activation deficits in dimensional anxious depression as detected by magnetoencephalography. Acta Neuropsychiatr 2015;27:143–52. 10.1017/neu.2014.46
    1. Glaus J, Vandeleur CL, von Känel R, et al. . Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study. J Psychiatr Res 2014;58:36–45. 10.1016/j.jpsychires.2014.07.012
    1. Karlović D, Serretti A, Vrkić N, et al. . Serum concentrations of CRP, IL-6, TNF-α and cortisol in major depressive disorder with melancholic or atypical features. Psychiatry Res 2012;198:74–80. 10.1016/j.psychres.2011.12.007
    1. Spanemberg L, Caldieraro M, Arrua Vares E, et al. . Biological differences between melancholic and nonmelancholic depression subtyped by the core measure. Neuropsychiatr Dis Treat 2014;10:1523–31. 10.2147/NDT.S66504
    1. Lamers F, Vogelzangs N, Merikangas KR, et al. . Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 2013;18:692–9. 10.1038/mp.2012.144
    1. Simmons WK, Burrows K, Avery JA, et al. . Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states. Mol Psychiatry 2020;25:1457–68. 10.1038/s41380-018-0093-6
    1. Yang C, Tiemessen KM, Bosker FJ, et al. . Interleukin, tumor necrosis factor-α and C-reactive protein profiles in melancholic and non-melancholic depression: a systematic review. J Psychosom Res 2018;111:58–68. 10.1016/j.jpsychores.2018.05.008
    1. Veltman EM, Lamers F, Comijs HC, et al. . Inflammatory markers and cortisol parameters across depressive subtypes in an older cohort. J Affect Disord 2018;234:54–8. 10.1016/j.jad.2018.02.080
    1. Zimmerman M, Clark H, McGonigal P, et al. . Reliability and validity of the DSM-5 anxious distress specifier interview. Compr Psychiatry 2017;76:11–17. 10.1016/j.comppsych.2017.02.010
    1. Shim IH, Woo YS, Bahk W-M. Associations between immune activation and the current severity of the "with anxious distress" specifier in patients with depressive disorders. Gen Hosp Psychiatry 2016;42:27–31. 10.1016/j.genhosppsych.2016.07.003
    1. Baek JH, Kim H-J, Fava M, et al. . Reduced venous blood basophil count and anxious depression in patients with major depressive disorder. Psychiatry Investig 2016;13:321–6. 10.4306/pi.2016.13.3.321
    1. Menke A, Lehrieder D, Fietz J, et al. . Childhood trauma dependent anxious depression sensitizes HPA axis function. Psychoneuroendocrinology 2018;98:22–9. 10.1016/j.psyneuen.2018.07.025
    1. Gaspersz R, Lamers F, Wittenberg G, et al. . The role of anxious distress in immune dysregulation in patients with major depressive disorder. Transl Psychiatry 2017;7:1268. 10.1038/s41398-017-0016-3
    1. Karlović D, Serretti A, Vrkić N, et al. . Serum concentrations of CRP, IL-6, TNF-α and cortisol in major depressive disorder with melancholic or atypical features. Psychiatry Res 2012;198:74–80. 10.1016/j.psychres.2011.12.007
    1. Glaus J, von Känel R, Lasserre AM, et al. . Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study. Psychol Med 2018;48:961–73. 10.1017/S0033291717002744
    1. Liu X, Wang Y, Peng D, et al. . The developmental and translational study on biomarkers and clinical characteristics-based diagnostic and therapeutic identification of major depressive disorder: study protocol for a multicenter randomized controlled trial in China. Neuropsychiatr Dis Treat 2020;16:2343–51. 10.2147/NDT.S271842
    1. Arnow BA, Blasey C, Williams LM, et al. . Depression subtypes in predicting antidepressant response: a report from the iSPOT-D trial. Am J Psychiatry 2015;172:743–50. 10.1176/appi.ajp.2015.14020181
    1. Stewart JW, McGrath PJ, Fava M, et al. . Do atypical features affect outcome in depressed outpatients treated with citalopram? Int J Neuropsychopharmacol 2010;13:15–30. 10.1017/S1461145709000182
    1. Duivis HE, de Jonge P, Penninx BW, et al. . Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. Am J Psychiatry 2011;168:913–20. 10.1176/appi.ajp.2011.10081163
    1. Huang W, Luo S, Burgess R, et al. . New insights into the tumor microenvironment utilizing protein array technology. Int J Mol Sci 2018;19:559. 10.3390/ijms19020559
    1. Rodney T, Osier N, Gill J. Pro- and anti-inflammatory biomarkers and traumatic brain injury outcomes: a review. Cytokine 2018;110:248–56. 10.1016/j.cyto.2018.01.012
    1. Chaturvedi SK, Manche Gowda S, Ahmed HU, et al. . More anxious than depressed: prevalence and correlates in a 15-nation study of anxiety disorders in people with type 2 diabetes mellitus. Gen Psychiatr 2019;32:e100076. 10.1136/gpsych-2019-100076
    1. Mohammed AA, Moustafa HA, Nour-Eldein H, et al. . Association of anxiety-depressive disorders with irritable bowel syndrome among patients attending a rural family practice center: a comparative cross-sectional study. Gen Psychiatr 2021;34:e100553. 10.1136/gpsych-2021-100553
    1. Loeffler A, Steptoe A. Bidirectional longitudinal associations between loneliness and pain, and the role of inflammation. Pain 2021;162:930–7. 10.1097/j.pain.0000000000002082

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren