Childhood infection and adult schizophrenia: a meta-analysis of population-based studies.

Objective: To determine whether exposures to infectious illness during childhood involving the CNS or elsewhere is associated with adult schizophrenia or other psychoses.

Method: Systematic review and meta-analysis of published literature identified by electronic and manual search meeting three inclusion criteria: population-base, objective assessment of childhood infection at the individual level, standard definition of adult psychotic outcomes. We calculated risk ratio for all CNS infection, and separately for viral and bacterial infection in relation to non-affective psychosis and schizophrenia, which was combined in meta-analysis.

Results: Seven studies were included. Meta-analysis involving 2424 cases and over 1.2 million controls showed CNS viral infection was associated with nearly two-fold increased risk of adult non-affective psychosis (risk ratio 1.70; 95% CI 1.13-2.55; p=0.01). There was no significant heterogeneity between studies (p=0.26; I(2)=20%). Separate meta-analysis involving 1035 cases and over 1.2 million controls suggested all childhood CNS infections, particularly viral infections, may be associated with nearly two-fold risk of adult schizophrenia. However, there was evidence of some heterogeneity between these studies (p=0.07; I(2)=70%). CNS bacterial infections were not associated with risk of psychosis. Data on childhood infections with no obvious involvement of the CNS is insufficient.

Conclusions: These findings indicate childhood CNS viral infections increase the risk of adult psychotic illness. Possible mechanisms may include both direct effects of pathogens, and the effects of inflammatory response on the developing brain.