Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Feb;43(2):239-57.
doi: 10.1017/S0033291712000736. Epub 2012 Apr 16.

Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies

G M Khandaker  1 , J Zimbron, G Lewis, P B Jones
Affiliations
Free PMC article
Review

Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies

G M Khandaker et al. Psychol Med. 2013 Feb.
Free PMC article

Abstract

Background: Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies.

Method: Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review.

Results: Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two- to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia.

Conclusions: Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Study selection process for the systematic review.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Albert LJ, Inman RD. Molecular mimicry and autoimmunity. New England Journal of Medicine. 1999;341:2068–2074. - PubMed
    1. Babulas V, Factor-Litvak P, Goetz R, Schaefer CA, Brown AS. Prenatal exposure to maternal genital and reproductive infections and adult schizophrenia. American Journal of Psychiatry. 2006;163:927–929. - PubMed
    1. Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993;341:938–941. - PubMed
    1. Bocchio Chiavetto L, Boin F, Zanardini R, Popoli M, Michelato A, Bignotti S, Tura GB, Gennarelli M. Association between promoter polymorphic haplotypes of interleukin-10 gene and schizophrenia. Biological Psychiatry. 2002;51:480–484. - PubMed
    1. Bradley AJ, Dinan TG. A systematic review of hypothalamic-pituitary-adrenal axis function in schizophrenia: implications for mortality. Journal of Psychopharmacology. 2010;24:91–118. - PubMed

MeSH terms