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Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study

Published online by Cambridge University Press:  20 February 2015

M. Virtanen*
Affiliation:
Finnish Institute of Occupational Health, Helsinki, Finland
M. J. Shipley
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK
G. D. Batty
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
M. Hamer
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK
C. L. Allan
Affiliation:
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
G. D. Lowe
Affiliation:
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
K. P. Ebmeier
Affiliation:
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
T. N. Akbaraly
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK Inserm, U1198, Montpellier, France EPHE, Paris, France University Montpellier 2, Montpellier, France
H. Alenius
Affiliation:
Finnish Institute of Occupational Health, Helsinki, Finland
R. Haapakoski
Affiliation:
Finnish Institute of Occupational Health, Helsinki, Finland Department of Epidemiology and Public Health, University College London, London, UK Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
A. Singh-Manoux
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK Inserm, U1018, AP-HP, Villejuif, France
M. Kivimäki
Affiliation:
Department of Epidemiology and Public Health, University College London, London, UK
*
*Address for correspondence: M. Virtanen, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland. (Email: [email protected])

Abstract

Background

Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear.

Method

We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress.

Results

Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06–1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03–1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution.

Conclusions

IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Anderson, G, Kubera, M, Duda, W, Lason, W, Berk, M, Maes, M (2013). Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression. Pharmacological Reports 65, 16471654.Google Scholar
Cattaneo, A, Gennarelli, M, Uher, R, Breen, G, Farmer, A, Aitchison, KJ, Craig, IW, Anacker, C, Zunsztain, PA, McGuffin, P, Pariante, CM (2013). Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology 38, 377385.Google Scholar
Dantzer, R, O'Connor, JC, Freund, GG, Johnson, RW, Kelley, KW (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews. Neuroscience 9, 4656.Google Scholar
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK, Lanctot, KL (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446457.Google Scholar
Duivis, HE, de Jonge, P, Penninx, BW, Na, BY, Cohen, BE, Whooley, MA (2011). Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. American Journal of Psychiatry 168, 913920.Google Scholar
Goldberg, D, Williams, P (1988). A User's Guide to the General Health Questionnaire. NFER-Nelson Publishing Co.: Windsor, Berkshire.Google Scholar
Goldberg, DP (1972). The Detection of Psychiatric Illness by Questionnaire. Oxford University Press: London.Google Scholar
Hannestad, J, DellaGioia, N, Bloch, M (2011). The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36, 24522459.Google Scholar
Head, J, Stansfeld, SA, Ebmeier, KP, Geddes, JR, Allan, CL, Lewis, G, Kivimäki, M (2013). Use of self-administered instruments to assess psychiatric disorders in older people: validity of the General Health Questionnaire, the Center for Epidemiologic Studies Depression Scale and the self-completion version of the revised Clinical Interview Schedule. Psychological Medicine 43, 26492656.Google Scholar
Hiles, SA, Baker, AL, de Malmanche, T, Attia, J (2012). Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychological Medicine 42, 20152026.CrossRefGoogle ScholarPubMed
Howren, MB, Lamkin, DM, Suls, J (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171186.Google Scholar
Janssen, DG, Caniato, RN, Verster, JC, Baune, BT (2010). A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Human Psychopharmacology 25, 201215.Google Scholar
Kivimaki, M, Shipley, MJ, Batty, GD, Hamer, M, Akbaraly, TN, Kumari, M, Jokela, M, Virtanen, M, Lowe, GD, Ebmeier, KP, Brunner, EJ, Singh-Manoux, A (2014). Long-term inflammation increases risk of common mental disorder: a cohort study. Molecular Psychiatry 19, 149150.Google Scholar
Lanquillon, S, Krieg, JC, Bening-Abu-Shach, U, Vedder, H (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22, 370379.Google Scholar
Maes, M, Leonard, BE, Myint, AM, Kubera, M, Verkerk, R (2011). The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Progress in Neuro-Psychopharmacol and Biological Psychiatry 35, 702721.Google Scholar
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732741.Google Scholar
Muller, N (2014). Immunology of major depression. Neuroimmunomodulation 21, 123130.Google Scholar
Myint, AM, Schwarz, MJ, Muller, N (2012). The role of the kynurenine metabolism in major depression. Journal of Neural Transmission 119, 245251.Google Scholar
O'Brien, SM, Scully, P, Fitzgerald, P, Scott, LV, Dinan, TG (2007). Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. Journal of Psychiatric Research 41, 326331.Google Scholar
Raison, CL, Miller, AH (2013). The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D). Molecular Psychiatry 18, 1537.Google Scholar
Tabak, AG, Jokela, M, Akbaraly, TN, Brunner, EJ, Kivimäki, M, Witte, DR (2009). Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II Study. Lancet 373, 22152221.Google Scholar
Tunstall-Pedoe, H, Kuulasmaa, K, Amouyel, P, Arveiler, D, Rajakangas, AM, Pajak, A (1994). Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 90, 583612.Google Scholar
Valkanova, V, Ebmeier, KP, Allan, CL (2013). CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders 150, 736744.Google Scholar
Yang, JJ, Wang, N, Yang, C, Shi, JY, Yu, HY, Hashimoto, K (2015). Serum interleukin-6 is a predictive biomarker for ketamine's antidepressant effect in treatment-resistant patients with major depression. Biological Psychiatry 77, e19e20.Google Scholar
Yoshimura, R, Hori, H, Ikenouchi-Sugita, A, Umene-Nakano, W, Ueda, N, Nakamura, J (2009). Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 33, 722726.Google Scholar
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