Antipsychotics' effects on blood levels of cytokines in schizophrenia: A meta-analysis
Abstract
Objectives Evidence-based medicine suggests that schizophrenia is associated with an inflammatory syndrome, but the extent to which this syndrome is normalized by antipsychotic treatment has yet to be determined.Methods A systematic quantitative review of the effects of antipsychotics on peripheral cytokine levels in schizophrenia was performed, using follow-up studies providing in vivo cytokine assessments before and after treatment.Results We retrieved 23 studies (total of 762 subjects) which showed that antipsychotic treatment significantly increases plasma levels of soluble interleukin-2 receptor and reduces the plasma levels of interleukin-1β and interferon-γ.Conclusions These results show that antipsychotics produce anti-inflammatory effects in schizophrenia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-6 has inconsistent findings in SCZ pre- and post-treatment comparison.
“For example, IL-6 has inconsistent findings in SCZ pre- and post-treatment comparison41,42,”
From Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses (2019) · cites this paper as [41]
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
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 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2009.06.005 · Cited by 19,575 · see citing works
Duval, S., & Tweedie, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00455.x · Cited by 14,099 · see citing works
Wasserman, S. S., Hedges, L. V., & Olkin, I. (1988) · Journal of Educational Statistics · doi:10.2307/1164953 · Cited by 10,347 · see citing works
(2000) · Cited by 9,198 · see citing works
Statistical Methods for Meta-Analysis.
Freeman, P. R., Hedges, L. V., & Olkin, I. (1986) · Biometrics · doi:10.2307/2531069 · Cited by 4,832 · see citing works
The Handbook of Research Synthesis and Meta-Analysis
(2019) · doi:10.7758/9781610448864 · Cited by 4,553 · see citing works
Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality
McGrath, J., Saha, S., Chant, D., & Welham, J. (2008) · Epidemiologic Reviews · doi:10.1093/epirev/mxn001 · Cited by 2,280 · see citing works
TNF-mediated inflammatory disease
Bradley, Jr. (2008) · The Journal of Pathology · doi:10.1002/path.2287 · Cited by 2,094 · see citing works
Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.013 · Cited by 1,742 · see citing works
Paulson, J. F., & Bazemore, S. D. (2010) · JAMA · doi:10.1001/jama.2010.605 · Cited by 1,337 · see citing works
IL-12 family cytokines: immunological playmakers
Vignali, D. A. A., & Kuchroo, V. K. (2012) · Nature Immunology · doi:10.1038/ni.2366 · Cited by 1,295 · see citing works
Inflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review
Potvin, S., Stip, É., Sepehry, A. A., Gendron, A., Bah, R., & Kouassi, É. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.024 · Cited by 989 · see citing works
Self-citationMaes, M. H. J., Bosmans, E., Calabrese, J. R., Smith, R. S., & Meltzer, H. Y. (1995) · Journal of Psychiatric Research · doi:10.1016/0022-3956(94)00049-w · Cited by 385 · see citing works
Cytokines in schizophrenia and the effects of antipsychotic drugs
Drzyzga, Ł. R., Obuchowicz, E., Marcinowska, A., & Herman, Z. S. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.02.002 · Cited by 242 · see citing works
Zhang, X. Y., Zhou, D. F., Cao, L. Y., Wu, G. Y., & Shen, Y. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300756 · Cited by 208 · see citing works
Autoimmune diseases and infections as risk factors for schizophrenia
Benros, M. E., Mortensen, P. B., & Eaton, W. W. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06638.x · Cited by 190 · see citing works
Th1, Th2 and Th3 cytokine alteration in schizophrenia
Kim, Y., Myint, A.-M., Lee, B.-H., Han, C.-S., Lee, H., Kim, D.-J., & Leonard, B. E. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.047 · Cited by 187 · see citing works
The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia
Song, X., Lv, L., Li, W., Hao, Y., & Zhao, J. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.018 · Cited by 187 · see citing works
Maes, M. H. J. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(00)00094-3 · Cited by 179 · see citing works
In vivo immunomodulatory effects of clozapine in schizophrenia
Maes, M. H. J., Bosmans, E., Kenis, G., Jong, R. D., Smith, R. S., & Meltzer, H. Y. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(97)00057-1 · Cited by 178 · see citing works
Kim, Y., Kim, L., & Lee, M. (2000) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00171-1 · Cited by 159 · see citing works
Maes, M. (2000) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(99)00062-0 · Cited by 156 · see citing works
Kim, Y., Myint, A.-M., Verkerk, R. M., Scharpé, S., Steinbusch, H. W. M., & Leonard, B. E. (2009) · Neuropsychobiology · doi:10.1159/000213565 · Cited by 136 · see citing works
Monteleone, P., Fabrazzo, M., Tortorella, A. A. V., & Maj, M. (1997) · Psychiatry Research · doi:10.1016/s0165-1781(97)00036-x · Cited by 134 · see citing works
Müller, N., Empl, M., Riedel, M. J., Schwarz, M., & Ackenheil, M. (1997) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02922260 · Cited by 127 · see citing works
Akiyama, K. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(98)00140-6 · Cited by 109 · see citing works
Hori, H., Yoshimura, R., Yamada, Y., Ikenouchi, A., Mitoma, M., Ida, Y., & Nakamura, J. (2007) · PubMed · doi:10.1097/yic.0b013e3280103593 · Cited by 83 · see citing works
Zhang, X. Y., Zhou, D. F., Qi, L. Y., Chen, S., Cao, L. Y., Chen, D. C., Xiu, M. H., Wang, F., Wu, G. Y., Lü, L., et al. (2009) · Psychopharmacology · doi:10.1007/s00213-008-1447-6 · Cited by 81 · see citing works
Hinze‐Selch, D., Deuschle, M., Weber, B., Heuser, I., & Pollmächer, T. (2000) · Psychopharmacology · doi:10.1007/s002139900351 · Cited by 75 · see citing works
Antipsychotic treatment may alter T-helper (TH) 2 arm cytokines
Pae, C., Yoon, C., Kim, T., Kim, J.-J., Park, S., Lee, C., Lee, S.-J., Lee, C., & Paik, I. (2005) · International Immunopharmacology · doi:10.1016/j.intimp.2005.10.004 · Cited by 73 · see citing works
Bast, T. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.01.003 · Cited by 72 · see citing works
Clozapine-Induced Increase in Plasma Levels of Soluble Interleukin-2 Receptors
Pollmächer, T. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950220087016 · Cited by 69 · see citing works
Crespo‐Facorro, B., Carrasco-Marı́n, E., Pérez‐Iglesias, R., Pelayo‐Terán, J. M., Fernández-Prieto, L., Leyva‐Cobián, F., & Vázquez‐Barquero, J. L. (2008) · Psychiatry Research · doi:10.1016/j.psychres.2006.08.005 · Cited by 55 · see citing works
Pacheco, R., Riquelme, E. M., & Kalergis, A. M. (2010) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152410790780154 · Cited by 54 · see citing works
Sirota, P., Meiman, M. E., Hershko, R., & Bessler, H. (2005) · Psychiatry Research · doi:10.1016/j.psychres.2004.04.012 · Cited by 51 · see citing works
Effect of Risperidone on Serum Cytokines
Kim, D., Kim, W. B., Yoon, S.-J., Go, H.-J., Choi, B., Jun, T., & Kim, Y. (2001) · International Journal of Neuroscience · doi:10.3109/00207450108986549 · Cited by 50 · see citing works
Sarandöl, A., Kırlı, S., Akkaya, C., Ocak, N., Eröz, E., & Sarandöl, E. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107077609 · Cited by 42 · see citing works
Baptista, T., Sandia, I., Lacruz, A., Rangel, N., Mendoza, S., Beaulieu, S., Contreras, Q., Galeazzi, T., & Vargas, D. (2007) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32801182e6 · Cited by 32 · see citing works
Increased interleukin-6 level in Taiwanese schizophrenic patients.
Lin, C.-C., Chang, C., Chang, P.-Y., & Huang, T. (2011) · PubMed · Cited by 29 · see citing works
Igué, R., Potvin, S., Bah, R., Stip, É., Bouchard, R.-H., Lipp, O., Gendron, A., & Kouassi, É. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.05.011 · Cited by 29 · see citing works
Self-citationLong-term course and outcome in schizophrenia: a 34-year follow-up study in Alberta, Canada
Newman, S. C., Bland, R. C., & Thompson, A. (2012) · Psychological Medicine · doi:10.1017/s0033291712000177 · Cited by 25 · see citing works
In vivo immunomodulatory effects of antipsychotics on inflammatory mediators: A review
Tourjman, V., Koué, M.-È., Kouassi, É., & Potvin, S. (2012) · Advances in Bioscience and Biotechnology · doi:10.4236/abb.2012.324072 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Goldsmith, D. R., Rapaport, M. H., & Miller, B. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.3 · Cited by 1,683 · see citing works
Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders
Fiorentino, M., Sapone, A., Senger, S., Camhi, S. S., Kadzielski, S. M., Buie, T. M., Kelly, D. L., Cascella, N., & Fasano, A. (2016) · Molecular Autism · doi:10.1186/s13229-016-0110-z · Cited by 494 · see citing works
Yuan, N., Chen, Y., Xia, Y., Dai, J., & Liu, C. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0570-y · Cited by 428 · see citing works
Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis
Mondelli, V., Ciufolini, S., Belvederi Murri, M., Bonaccorso, S., Di Forti, M., Giordano, A., Marques, T. R., Zunszain, P. A., Morgan, C., Murray, R. M., et al. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv028 · Cited by 286 · see citing works
Neuroinflammation in schizophrenia: meta-analysis of <i>in vivo</i> microglial imaging studies
Marques, T. R., Ashok, A. H., Pillinger, T., Veronese, M., Turkheimer, F. E., Dazzan, P., Sommer, I. E. C., & Howes, O. D. (2019) · Psychological Medicine · doi:10.1017/s0033291718003057 · Cited by 213 · see citing works
Baumeister, D., Ciufolini, S., & Mondelli, V. (2016) · Psychopharmacology · doi:10.1007/s00213-015-4044-5 · Cited by 183 · see citing works
Capuzzi, E., Bartoli, F., Crocamo, C., Clerici, M., & Carrà, G. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.003 · Cited by 139 · see citing works
Prata, J., Santos, S. G., Almeida, M. I., Coelho, R., & Barbosa, M. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0938-y · Cited by 115 · see citing works
de Bartolomeis, A., Barone, A., Vellucci, L., Mazza, B., Austin, M. C., Iasevoli, F., & Ciccarelli, M. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02976-3 · Cited by 113 · see citing works
The Role of Cytokines in the Pathogenesis of Schizophrenia
Dawidowski, B., Górniak, A., Podwalski, P., Lebiecka, Z., Misiak, B., & Samochowiec, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173849 · Cited by 102 · see citing works
Juncal-Ruiz, M., Riesco-Dávila, L., Ortiz-García de la Foz, V., Martínez-Garcia, O., Ramírez-Bonilla, M., Ocejo-Viñals, J. G., Leza, J. C., López-Hoyos, M., & Crespo-Facorro, B. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.06.039 · Cited by 55 · see citing works
Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers
Handley, R., Mondelli, V., Zelaya, F., Marques, T., Taylor, H., Reinders, A. A. T. S., Chaddock, C., McQueen, G., Hubbard, K., Papadopoulos, A., et al. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.03.039 · Cited by 42 · see citing works
Increased IL-3 Serum Levels in Chronic Patients with Schizophrenia: Associated with Psychopathology
Xiu, M. H., Lin, C. G., Tian, L., Tan, Y. L., Chen, J., Chen, S., Tan, S. P., Wang, Z. R., Yang, F. D., Chen, D. C., et al. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.07.029 · Cited by 27 · see citing works
- Authors
- Tourjman, V., Kouassi, É., Koué, M.-È., Rocchetti, M., Fortin-Fournier, S., Fusar-Poli, P., & Potvin, S.
- Affiliations
- Université de Montréal (CA)
- Hôpital Maisonneuve-Rosemont (CA)
- King's College London (GB)
- Institut universitaire en santé mentale de Montréal (CA)
- Corresponding author
- Kouassi, Édouard
- Potvin, Stéphane
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 151
- Issue
- 1-3
- Pages
- 43-47
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2166043067
- Cited by
- 224
- References
- 45
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 12 · 2023: 27 · 2022: 15 · 2021: 20 · 2020: 15 · 2019: 16 · 2018: 19 · 2017: 18 · 2016: 26 · 2015: 21 · 2014: 15
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- antipsychotic drugs, schizophrenia
- MeSH terms
- Humans, Schizophrenia, Antipsychotic Agents, Databases, Bibliographic, Cytokines, Evidence-Based Medicine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
