Schizophrenia and the Immune System

Pathophysiology, Prevention, and Treatment

Michelle D. Richard and Nancy C. Brahm


Am J Health Syst Pharm. 2012;69(9):757-766. 

In This Article

Abstract and Introduction


Purpose Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments.
Summary A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent.
Conclusion The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.


Schizophrenia is a devastating disorder with severe emotional, physical, and financial consequences for patients and their support networks. According to the National Institute of Mental Health, approximately 1% of Americans have a diagnosis of schizophrenia;[1] however, it is very difficult to estimate accurately the incidence and prevalence of this disorder due to the heterogeneity of signs and symptoms. Tandon and associates[2] postulated that "schizophrenia is probably neither a single disease entity and nor is it a circumscribed syndrome—it is likely to be a conglomeration of phenotypically similar disease entities and syndromes."

Given the impact of schizophrenia, it is crucial to develop a better understanding of schizophrenia pathophysiology, as well as possible methods of preventing and managing the disorder. This article explores the potential link between immune system dysfunction and schizophrenia, proposes a theoretical model to explain the plausibility of such a link, and discusses prevention and treatment implications for patients who may be at risk for or have immune system dysfunction-related schizophrenia.


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