Golam Khandaker1, Christina Dalman2,3, Nils Kappelmann1, Jan Stochl1, Henrik Dal3, Kyriaki Kosidou2,3, Peter Jones1, Håkan Karlsson2; 1University of Cambridge, 2Karolinska Institutet, 3Stockholm County Council
Using population-based longitudinal Swedish data (N=647,515), we tested (1) association of childhood infection with IQ and adult non-affective psychosis (NAP); (2) whether shared familial confounding explains the infection-NAP and IQ-NAP relationships; (3) whether IQ mediates and/or moderates the infection-NAP relationship. IQ was assessed at conscription around age 18 years. Data on hospitalisation with any infection from age 0–13 years, and hospitalisation with an ICD diagnosis of NAP in adulthood were retrieved from admission register. 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. 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.
