Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment
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Aim: Over the past several decades, there has been a growing research interest in the role of inflammation in the pathogenesis of schizophrenia. This review aims to summarize evidence in support of this relationship, to discuss biological mechanisms that might explain it, and to explore the translational impact by examining evidence from trials of anti‐inflammatory and immunomodulatory agents in the treatment of schizophrenia. Methods: This narrative review of the literature summarizes evidence from observational studies, clinical trials and meta‐analyses to evaluate the role of inflammation in the pathogenesis of schizophrenia and to discuss associated implications for treatment. Results: Epidemiological evidence and animal models support a hypothesis of maternal immune activation during pregnancy, which increases the risk of schizophrenia in the offspring. Several biomarker studies have found associations between classical pro‐inflammatory cytokines and schizophrenia. The precise biological mechanisms by which inflammatory processes might contribute to the pathogenesis of schizophrenia remain unclear, but likely include the actions of microglia and the complement system. Importantly, several trials provide evidence that certain anti‐inflammatory and immunomodulatory agents show beneficial effects in the treatment of schizophrenia. Nevertheless, there is a need for further precision‐focused basic science and translational research. Conclusions: Increasing our understanding of the role of inflammation in schizophrenia will enable novel opportunities for therapeutic and preventative interventions that are informed by the underlying pathogenesis of this complex disorder.
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Descent into schizophrenic illness is accompanied by accelerated gray matter loss and signs of inflammation.
“As the descent into schizophrenic illness is accompanied by accelerated gray matter loss and signs of inflammation (Mongan, Ramesar, Föcking, Cannon, & Cotter, 2019)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Mongan, Ramesar, Föcking, Cannon, & Cotter, 2019
Cites
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
Varese, F., Smeets, F., Drukker, M., Lieverse, R., Lataster, T., Viechtbauer, W., Read, J., van Os, J., & Bentall, R. P. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs050 · Cited by 2,436 · 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
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
Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies
Brown, A. S., & Derkits, E. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09030361 · Cited by 1,269 · see citing works
Maternal immune activation: Implications for neuropsychiatric disorders
Estes, M. L., & McAllister, A. K. (2016) · Science · doi:10.1126/science.aag3194 · Cited by 1,206 · see citing works
Minocycline: Far beyond an Antibiotic
Garrido‐Mesa, N., Zarzuelo, A., & Gálvez, J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12139 · Cited by 935 · see citing works
Amminger, G. P., Schäfer, M. R., Papageorgiou, K., Klier, C. M., Cotton, S. M., Harrigan, S. M., Mackinnon, A., McGorry, P. D., & Berger, G. E. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.192 · Cited by 896 · see citing works
Khandaker, G. M., Pearson, R. M., Zammit, S., Lewis, G., & Jones, P. B. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1332 · Cited by 846 · see citing works
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594 · see citing works
New insights on the role of microglia in synaptic pruning in health and disease
Hong, S., Dissing-Olesen, L., & Stevens, B. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.004 · Cited by 557 · see citing works
Cytokine function in medication-naive first episode psychosis: A systematic review and meta-analysis
Upthegrove, R., Manzanares-Teson, N., & Barnes, N. M. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.03.005 · Cited by 501 · see citing works
The promise of N-acetylcysteine in neuropsychiatry
Berk, M., Malhi, G. S., Gray, L. J., & Dean, O. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.01.001 · Cited by 434 · see citing works
Fillman, S. G., Weickert, T. W., Lenroot, R. K., Catts, S. V., Bruggemann, J. M., Catts, V. S., & Weickert, C. S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.90 · Cited by 270 · see citing works
Severance, E. G., Gressitt, K. L., Stallings, C. R., Origoni, A. E., Khushalani, S., Leweke, F. M., Dickerson, F. B., & Yolken, R. H. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.05.018 · Cited by 243 · see citing works
Perkins, D. O., Jeffries, C. D., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., Mathalon, D. H., McGlashan, T. H., Seidman, L. J., et al. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu099 · Cited by 238 · see citing works
Bordt, E. A., & Polster, B. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.033 · Cited by 202 · see citing works
Complement in the pathogenesis of Alzheimer’s disease
Morgan, B. P. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-017-0662-9 · Cited by 194 · see citing works
Alzheimer's disease: Innate immunity gone awry?
VanItallie, T. B. (2017) · Metabolism · doi:10.1016/j.metabol.2017.01.014 · Cited by 67 · see citing works
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Germann, M., Brederoo, S. G., & Sommer, I. E. C. (2021) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000696 · Cited by 102 · see citing works
Arnsten, A. F. T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107327 · Cited by 75 · see citing works
Hui, C. W., Vecchiarelli, H. A., Gervais, É., Luo, X., Michaud, F., Scheefhals, L., Bisht, K., Sharma, K., Topolnik, L., & Tremblay, M.-È. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.558181 · Cited by 64 · see citing works
- Authors
- Mongan, D., Ramesar, M., Föcking, M., Cannon, M., & Cotter, D.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Mongan, David
- Venue
- Early Intervention in Psychiatry
- Publisher
- Wiley
- Published
- 2019-07-31
- Volume
- 14
- Issue
- 4
- Pages
- 385-397
- ISSN
- 1751-7885 (ISSN-L)
- 1751-7893
- OpenAlex
- W2966662913
- Cited by
- 123
- References
- 21
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 27 · 2023: 19 · 2022: 24 · 2021: 14 · 2020: 9 · 2019: 2
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Early Intervention in Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- schizophrenia, neuroinflammation, maternal immune activation, inflammatory cytokines, microglia, complement system, anti-inflammatory agents, immunomodulators, schizophrenia pathogenesis, biomarkers
- MeSH terms
- Animals, Anti-Inflammatory Agents, Humans, Inflammation, Schizophrenia, Immunomodulation
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