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Review
. 2013 Apr 5:42:35-48.
doi: 10.1016/j.pnpbp.2012.02.001. Epub 2012 Feb 10.

Viral infection, inflammation and schizophrenia

Rachel E Kneeland  1 , S Hossein Fatemi
Affiliations
Review

Viral infection, inflammation and schizophrenia

Rachel E Kneeland et al. Prog Neuropsychopharmacol Biol Psychiatry. .

Abstract

Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia.

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Figures

Fig. 1
Fig. 1
a) Structure of the mouse placenta. The inset details the fetal–maternal interface in the labyrinth. b) Structure of the human placenta. The inset image shows a cross-section through the chorionic villus; trophoblast-derived structures (blue) and mesoderm-derived tissues (orange). The inset images illustrate the number and type of cell layers between the maternal and fetal blood. doi:10.1038/35080570. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics Volume 2, Edition 7, Rossant, J., Cross, J.C., Placental development: lessons from mouse mutants, 538–548, 2001.
Fig. 2
Fig. 2
Placental abnormalities following prenatal viral infection. a. labyrinth zone of placenta (60×) from sham-infected dam showing fetal blood space (FBS) and maternal blood space. Arrow points to an inflammatory cell. b. Junctional zone of placenta (20×) from infected dam showing presence of thrombosis (TH). ST, spongiotrophoblast cells. c. Junctional zone of placenta (40×) from infected dam showing disorganization of ST cells. d. Junctional zone of placenta (60×) from infected dam showing presence of TH and inflammatory cells (arrows). Reprinted from Neuropharmacology, Fatemi, S.H., Folsom, T.D., Rooney, R.J., Mori, S., Kornfield, T.E., Reutiman, T.J., Kneeland, R.E., Liesch, S.B., Hua, K., Hsu, J., Patel, D.H., The viral theory of schizophrenia revisited: Abnormal placental gene expression and structural changes with lack of evidence for H1N1 viral presence in placentae of infected mice or brains of exposed offspring, 2012, with permission from Elsevier.
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