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A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: Exploring the causes of heterogeneity
Open accessAbstract
Epidemiological evidence for the inflammatory hypothesis of depression is largely cross-sectional; people with depression have elevated levels of circulating pro-inflammatory markers compared to people without depression. The limitation of cross sectional research is the potential for extraneous factors to influence observed effects. The purpose of this meta-analysis of cross-sectional studies of interleukin(IL)-6 and IL-10 in people with and without depression is to provide a targeted analysis of potential moderator factors relating to the diagnosis of depression and to physical and psychiatric comorbidity. Electronic searches of Embase and Medline databases were conducted using subject headings "interleukin-6" or "interleukin-10" and those relating to depression. Studies were included if they measured circulating marker levels in serum or plasma in a group of people with and without depressive symptoms (99 studies for IL-6, 19 studies for IL-10). IL-6 was elevated in depressed compared to non-depressed groups (d = 0.46, 99% CI 0.34 to 0.58, I(2) = 85.9%). This effect was larger in subgroups where depressive disorders were diagnosed compared to those with only depressive symptoms via standardized inventory, and subgroups where participants were recruited from inpatient or outpatient settings compared to the general community. The effect was also larger in those who were not selected for a particular comorbidity compared to those selected for cardiovascular disease. IL-10 effect size was not significant (d = -0.31, 99% CI -0.95 to 0.32, I(2) = 94.1%) which was not accounted for in subgroup analyses or meta-regression, indicating there is not a global elevation in cytokines. These data highlight that comorbidity and behavioral aspects of depression need to be measured and controlled in future prospective and experimental research testing the inflammatory hypothesis of depression.
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“compared to nondepressed individuals, depressed individuals (who are otherwise healthy) exhibit higher circulating levels of several proinflammatory cytokines including IL-1, IL-6, and TNFα , as well as higher levels of the systemic inflammatory biomarker CRP”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Hiles, Baker, de Malmanche, & Attia, 2012
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“at least one study found that concentrations of the anti-inflammatory cytokine IL-10 are lower for depressed than for nondepressed individuals”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Hiles et al., 2012
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Citations
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009) · doi:10.1002/9780470743386 · Cited by 14,225
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2021) · doi:10.1002/9781119558378 · Cited by 9,799
The file drawer problem and tolerance for null results.
Rosenthal, R. (1979) · Psychological Bulletin · doi:10.1037/0033-2909.86.3.638 · Cited by 9,068
Estimating the mean and variance from the median, range, and the size of a sample
Hozo, S. P., Djulbegovic, B., & Hozo, I. (2005) · BMC Medical Research Methodology · doi:10.1186/1471-2288-5-13 · Cited by 9,062
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988
Inflammation and Atherosclerosis
Libby, P., Ridker, P. M., & Maseri, A. (2002) · Circulation · doi:10.1161/hc0902.104353 · Cited by 7,724
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
The regulation of IL-10 production by immune cells
Saraiva, M., & O’Garra, A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2711 · Cited by 3,293
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766
Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease
Ouyang, W., Rutz, S., Crellin, N. K., Valdez, P. A., & Hymowitz, S. G. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101312 · Cited by 2,004
Global burden of depressive disorders in the year 2000
Üstün, T. B., Ayuso-Mateos, J. L., Chatterji, S., Mathers, C., & Murray, C. J. L. (2004) · British Journal of Psychiatry · doi:10.1192/bjp.184.5.386 · Cited by 1,735
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365
Steptoe, A., Hamer, M., & Chida, Y. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.03.011 · Cited by 1,278
Mood disorders in the medically ill: scientific review and recommendations
Evans, D. L., Charney, D. S., Lewis, L., Golden, R. N., Gorman, J. M., Krishnan, K. R. R., Nemeroff, C. B., Bremner, J. D., Carney, R. M., Coyne, J. C., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.001 · Cited by 1,071
Tyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(05)67763-x · Cited by 1,069 · cited 2×
“Additionally, often in the context of general medical illness, randomized controlled trials have indicated that psychological or antidepressant treatment for depression may reduce pro-inflammatory markers and improve immune functioning, administration of antidepressants can reduce depression induced by treatment with…”
BackgroundObesity, inflammation, and atherosclerosis
Rocha, V. Z., & Libby, P. (2009) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2009.55 · Cited by 994
Depression and the risk for cardiovascular diseases: Systematic review and meta analysis
Van der Kooy, K., van Hout, H., Marwijk, H., Marten, H., Stehouwer, C., & Beekman, A. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1723 · Cited by 951
Liu, Y., Ho, R. C.-M., & Mak, A. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.08.003 · Cited by 948
Maes, M., Yirmyia, R., Noraberg, J., Brene, S., Hibbeln, J., Perini, G., Kubera, M., Bob, P., Lerer, B., & Maj, M. (2009) · Metabolic Brain Disease · doi:10.1007/s11011-008-9118-1 · Cited by 894
Müller, N., Schwarz, M. J., Dehning, S., Douhe, A., Cerovecki, A., Goldstein-Müller, B., Spellmann, I., Hetzel, G., Maino, K., Kleindienst, N., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001805 · Cited by 794
Depressive disorders and immunity: 20 years of progress and discovery
Irwin, M. R., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.01.010 · Cited by 676
Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565
O’Connor, M.-F., Bower, J. E., Cho, H. J., Creswell, J. D., Dimitrov, S., Hamby, M. E., Hoyt, M. A., Martin, J. L., Robles, T. F., Sloan, E. K., et al. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.04.005 · Cited by 500
Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial
Andersen, B. L., Farrar, W. B., Golden-Kreutz, D. M., Glaser, R., Emery, C. F., Crespin, T. R., Shapiro, C. L., & Carson, W. E. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.06.030 · Cited by 416
Tynan, R. J., Weidenhofer, J., Hinwood, M., Cairns, M. J., Day, T. A., & Walker, F. R. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.12.011 · Cited by 382
Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.12.007 · Cited by 381 · cited 2×
“, 2004), and cognitive problems and psychomotor slowing (Brydon et al., 2008; Reichenberg et al., 2001).”
BackgroundAssociation of high-sensitivity C-reactive protein with de novo major depression
Pasco, J. A., Nicholson, G. C., Williams, L. J., Jacka, F. N., Henry, M. J., Kotowicz, M. A., Schneider, H. G., Leonard, B. E., & Berk, M. (2010) · British Journal of Psychiatry · doi:10.1192/bjp.bp.109.076430 · Cited by 321
Cytokine levels in the blood may distinguish suicide attempters from depressed patients
Janelidze, S., Mattei, D., Westrin, Å., Träskman-Bendz, L., & Brundin, L. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.10.010 · Cited by 298
O’Donovan, A., Hughes, B. M., Slavich, G. M., Lynch, L., Cronin, M.-T., O’Farrelly, C., & Malone, K. M. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.03.003 · Cited by 296 · cited 1×
“For instance, adiposity is thought to considerably contribute to levels of circulating IL-6, vascular inflammation is thought to cause atherosclerosis, and anxiety is associated with increased levels of pro-inflammatory markers most likely via neuroendocrine and nervous system stress activation (O’Donovan et al., 2010…”
BackgroundInflammatory Markers and Sleep Disturbance in Major Depression
Motivala, S. J., Sarfatti, A., Olmos, L., & Irwin, M. R. (2005) · Psychosomatic Medicine · doi:10.1097/01.psy.0000149259.72488.09 · Cited by 286
Anxiety in relation to inflammation and coagulation markers, among healthy adults: The ATTICA Study
Pitsavos, C., Panagiotakos, D. B., Papageorgiou, C., Tsetsekou, E., Soldatos, C., & Stefanadis, C. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.06.001 · Cited by 283
Shelton, R. C., & Miller, A. H. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.04.004 · Cited by 264
Comorbid psychiatric disorders in depressed outpatients: Demographic and clinical features
Rush, A. J., Zimmerman, M. A., Wisniewski, S. R., D, M. F. M., Hollon, S. D., Warden, D., Biggs, M. M., Shores‐Wilson, K., Shelton, R. C., Luther, J. F., et al. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.03.005 · Cited by 261
Immunological effects of induced shame and guilt
Dickerson, S. S., Kemeny, M. E., Aziz, N., Kim, K. H., & Fahey, J. L. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000097338.75454.29 · Cited by 245
Dhabhar, F. S., Burke, H. M., Epel, E. S., Mellon, S. H., Rosser, R., Reus, V. I., & Wolkowitz, O. M. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.05.010 · Cited by 225
Hiles, S. A., Baker, A., de Malmanche, T., & Attia, J. (2012) · Psychological Medicine · doi:10.1017/s0033291712000128 · Cited by 224
Self-citationDuivis, H. E., de Jonge, P., Penninx, B. W., Na, B. Y., Cohen, B. E., & Whooley, M. A. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10081163 · Cited by 191
Maes, M. H. J., Mihaylova, I., Kubera, M., & Ringel, K. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.09.006 · Cited by 170
Cytokines and pathological sleep
Kapsimalis, F., Basta, M., Varouchakis, G., Gourgoulianis, K. I., Vgontzas, A. N., & Kryger, M. H. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2007.08.019 · Cited by 170
Capuron, L., Fornwalt, F. B., Knight, B. T., Harvey, P. D., Ninan, P. T., & Miller, A. H. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.02.017 · Cited by 164
IL-10 modulates depressive-like behavior
Mesquita, A. R., Correia‐Neves, M., Roque, S., Castro, A. G., Vieira, P., Pedrosa, J., Palha, J. A., & Sousa, N. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.02.004 · Cited by 159
Pizzi, C., Mancini, S., Angeloni, L., Fontana, F., Manzoli, L., & Costa, G. M. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.121 · Cited by 148
Different immune patterns in melancholic and non-melancholic major depression
Rothermundt, M., Arolt, V., Fenker, J., Gutbrodt, H., Peters, M., & Kirchner, H. (2001) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s004060170058 · Cited by 143
Differences in cytokines between non-suicidal patients and suicidal patients in major depression
Kim, Y.-K., Lee, S.-W., Kim, S.-H., Shim, S.-H., Han, S.-W., Choi, S.-H., & Lee, B.-H. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2007.08.041 · Cited by 140
Matthews, K. A., Schott, L. L., Bromberger, J. T., Cyranowski, J. M., Everson-Rose, S. A., & Sowers, M. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.08.005 · Cited by 132
Kraus, M. R., Schäfer, A., Schöttker, K., Keicher, C., Weißbrich, B., Hofbauer, I., & Scheurlen, M. (2007) · Gut · doi:10.1136/gut.2007.131607 · Cited by 118
Cytokine profiles in women with different subtypes of major depressive disorder
Marques-Deak, A., NETO, F., Dominguez, W. V., Solis, A. C. D. O., Kurcgant, D., Sato, F. P., Ross, J. M., & Prado, E. D. F. G. B. (2005) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2005.11.003 · Cited by 111
Association of peripheral inflammatory markers with chronic fatigue in a population-based sample
Raison, C. L., Lin, J.-M. S., & Reeves, W. C. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.11.005 · Cited by 108
Interleukin-10: A Key Cytokine in Depression?
Roque, S., Correia-Neves, M., Mesquita, A. R., Palha, J. A., & Sousa, N. (2009) · Cardiovascular Psychiatry and Neurology · doi:10.1155/2009/187894 · Cited by 89
Hamer, M., Molloy, G. J., de Oliveira, C., & Demakakos, P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.01.005 · Cited by 82
Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice
Toth, L. A., & Opp, M. R. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.6.r1806 · Cited by 75
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BackgroundPeripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies
Köhler, C. A., Freitas, T. H., Maes, M., de Andrade, N. Q., Liu, C. S., Fernandes, B. S., Stubbs, B., Solmi, M., Veronese, N., Herrmann, N., et al. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12698 · Cited by 1,443
Haapakoski, R., Mathieu, J., Ebmeier, K. P., Alenius, H., & Kivimäki, M. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.06.001 · Cited by 1,129
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Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073
Miller, A. H., Haroon, E., Raison, C. L., & Felger, J. C. (2013) · Depression and Anxiety · doi:10.1002/da.22084 · Cited by 892
Metadata
- Authors
- Hiles, S. A., Baker, A. L., de Malmanche, T., & Attia, J.
- Affiliations
- University of Newcastle Australia (AU)
- John Hunter Hospital (AU)
- Corresponding author
- Hiles, Sarah A.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 26
- Issue
- 7
- Pages
- 1180-1188
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1972846275
- Cited by
- 274
- References
- 56
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 11 · 2023: 21 · 2022: 31 · 2021: 15 · 2020: 18 · 2019: 28 · 2018: 21 · 2017: 24 · 2016: 22 · 2015: 20 · 2014: 19 · 2013: 16 · 2012: 3
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- depression, interleukin-6, IL-10, cytokines, depressive symptoms, comorbidities, cardiovascular disease
- MeSH terms
- Cross-Sectional Studies, Data Interpretation, Statistical, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Inflammation, Inpatients, Life Style, Outpatients, Interleukin-6, Comorbidity, Interleukin-10
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