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Prenatal inflammation and risk for schizophrenia: A role for immune proteins in neurodevelopment

Published online by Cambridge University Press:  02 August 2018

Dana M. Allswede  and
Tyrone D. Cannon
Dana M. Allswede*
Affiliation:
Yale University
Tyrone D. Cannon
Affiliation:
Yale University
*
Address correspondence and reprint requests to: Dana Allswede, Department of Psychology, Yale University, 2 Hillhouse Ave., PO Box 208205, New Haven, CT 06520; E-mail: dana.allswede@yale.edu.
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Abstract

Prenatal inflammation is an established risk factor for schizophrenia. However, the specific inflammatory pathways that mediate this association remain unclear. Potential candidate systems include inflammatory markers produced by microglia, such as cytokines and complement. Accumulating evidence suggests that these markers play a role in typical neurodevelopmental processes, such as synapse formation and interneuron migration. Rodent models demonstrate that altered marker levels during the prenatal period can cause lasting deficits in these systems, leading to cognitive deficits that resemble schizophrenia. This review assesses the potential role of prenatal cytokine and complement elevations on the etiology of schizophrenia. The current neurobiological understanding of the development of schizophrenia is reviewed to identify candidate cellular mechanisms that may be influenced by prenatal inflammation. We discuss the functions that cytokines and complement may play in prenatal neurodevelopment, review evidence that links exposure to these factors with risk for schizophrenia, and consider how these markers may interact with genetic vulnerabilities to influence the neurodevelopment of schizophrenia. We consider how prenatal inflammatory exposure may influence childhood and adolescent developmental risk trajectories for schizophrenia. Finally, we identify areas of further research needed to support the development of anti-inflammatory treatments to prevent the development of schizophrenia in at-risk neonates.

Type
Special Issue Articles
Information
Development and Psychopathology , Volume 30 , Special Issue 3: Developmental Origins of Psychopathology: Mechanisms, Processes, and Pathways Linking the Prenatal Environment to Postnatal Outcomes , August 2018 , pp. 1157 - 1178
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

We thank Avram Holmes and David Glahn for their comments on drafts of the manuscript. Dana Allswede's work was funded by National Science Foundation Graduate Research Fellowship DGE-1122492.

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