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Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

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Adrianna P. Kępińska, Conrad O. Iyegbe, Anthony C. Vernon, Robert Yolken, Robin M. Murray, Thomas A. Pollak

Original languageEnglish
Article number72
JournalFrontiers in Psychiatry
Early online date26 Feb 2020
Accepted/In press28 Jan 2020
E-pub ahead of print26 Feb 2020
Published26 Feb 2020


King's Authors


Associations between influenza infection and psychosis have been reported since the eighteenth century, with acute “psychoses of influenza” documented during multiple pandemics. In the late 20th century, reports of a season-of-birth effect in schizophrenia were supported by large-scale ecological and sero-epidemiological studies suggesting that maternal influenza infection increases the risk of psychosis in offspring. We examine the evidence for the association between influenza infection and schizophrenia risk, before reviewing possible mechanisms via which this risk may be conferred. Maternal immune activation models implicate placental dysfunction, disruption of cytokine networks, and subsequent microglial activation as potentially important pathogenic processes. More recent neuroimmunological advances focusing on neuronal autoimmunity following infection provide the basis for a model of infection-induced psychosis, potentially implicating autoimmunity to schizophrenia-relevant protein targets including the N-methyl-D-aspartate receptor. Finally, we outline areas for future research and relevant experimental approaches and consider whether the current evidence provides a basis for the rational development of strategies to prevent schizophrenia.

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