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

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.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry, University of Cambridge, UK. gmk24@medschl.cam.ac.uk

    , ,

    Source

    Psychological medicine 43:2 2013 Feb pg 239-57

    MeSH

    Adult
    Animals
    Autoimmunity
    Brain
    Confounding Factors (Epidemiology)
    Cytokines
    Databases, Bibliographic
    Disease Models, Animal
    Female
    Genetic Predisposition to Disease
    Humans
    Pregnancy
    Pregnancy Complications, Infectious
    Pregnancy Trimesters
    Prenatal Exposure Delayed Effects
    Risk Factors
    Schizophrenia

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    22717193

    Citation

    Khandaker, G M., et al. "Prenatal Maternal Infection, Neurodevelopment and Adult Schizophrenia: a Systematic Review of Population-based Studies." Psychological Medicine, vol. 43, no. 2, 2013, pp. 239-57.
    Khandaker GM, Zimbron J, Lewis G, et al. Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychol Med. 2013;43(2):239-57.
    Khandaker, G. M., Zimbron, J., Lewis, G., & Jones, P. B. (2013). Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychological Medicine, 43(2), pp. 239-57. doi:10.1017/S0033291712000736.
    Khandaker GM, et al. Prenatal Maternal Infection, Neurodevelopment and Adult Schizophrenia: a Systematic Review of Population-based Studies. Psychol Med. 2013;43(2):239-57. PubMed PMID: 22717193.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. AU - Khandaker,G M, AU - Zimbron,J, AU - Lewis,G, AU - Jones,P B, Y1 - 2012/04/16/ PY - 2012/6/22/entrez PY - 2012/6/22/pubmed PY - 2013/6/19/medline SP - 239 EP - 57 JF - Psychological medicine JO - Psychol Med VL - 43 IS - 2 N2 - 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. SN - 1469-8978 UR - https://www.unboundmedicine.com/medline/citation/22717193/full_citation L2 - https://www.cambridge.org/core/product/identifier/S0033291712000736/type/journal_article DB - PRIME DP - Unbound Medicine ER -