Childhood Infection, IQ and Risk of Non-affective Psychosis in Adulthood: A Swedish Population-based Longitudinal Cohort and Co-relative Study

23 Feb 2018

Importance: Associations between childhood infection, IQ and adult non-affective psychosis (NAP) are well established. However, examination of sensitive periods for exposure, effect of familial confounding, and whether IQ provides a link between childhood infection and adult NAP may elucidate pathogenesis of psychosis further. Objective: To test (1) association of childhood infection with IQ and adult NAP; (2) whether shared familial confounding explains the infection-NAP and IQ-NAP relationships; (3) whether IQ mediates and/or moderates the childhood infection-NAP relationship. Design, Setting and Participants: Longitudinal design using linkage of Swedish national registers. The risk set included all Swedish men born 1973–1992 and conscripted into military until end of 2010 (N=771,698). We included 647,515 participants in the analysis. Measurement of exposure: Hospitalisation with any infection from age 0–13 years. Main outcomes and measures: Hospitalisation with an ICD diagnosis of NAP until end of 2011. IQ was assessed at conscription around age 18 years. Results: Exposure to infections particularly in early-childhood was associated with lower IQ (adjusted mean difference for infection at 0-1y: -1.61; 95% CI, -1.74, -1.47), and with increased risk of adult NAP (adjusted hazard ratio for infection at 0-1y: 1.19; 95% CI, 1.06-1.33). There was a linear association between lower premorbid IQ and adult NAP, which persisted after excluding prodromal cases (adjusted hazard ratio per 1-point increase in IQ: 0.976; 95% CI, 0.974-0.978). The infection-NAP and IQ-NAP associations were similar in the general population and in full-sibling pairs discordant for exposure. IQ both moderated (P=0.02 and P=0.001) and mediated (P<0.001) the association between infection and NAP. Childhood infection had a greater impact on NAP risk in the lower, compared with higher, IQ range. Conclusions and Relevance: Early-childhood is a sensitive period for the effects of infection on IQ and NAP. The associations of adult NAP with early-childhood infection and adolescent IQ are not fully explained by shared familial factors, so may be causal. Lower premorbid IQ in psychosis arises from unique environmental factors, such as early-childhood infection. Early-childhood infections may increase risk of NAP by affecting neurodevelopment and by exaggerating the effects of cognitive vulnerability to psychosis.