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Background: Schizophrenia is associated with impaired neurodevelopment as indexed by lower premorbid IQ. We examined associations between erythrocyte sedimentation rate (ESR), a marker of low-grade systemic inflammation, IQ, and subsequent schizophrenia and other non-affective psychoses (ONAP) to elucidate the role of neurodevelopment and inflammation in the pathogenesis of psychosis. Methods: Population-based data on ESR and IQ from 638 213 Swedish men assessed during military conscription between 1969 and 1983 were linked to National Hospital Discharge Register for hospitalisation with schizophrenia and ONAP. The associations of ESR with IQ (cross-sectional) and psychoses (longitudinal) were investigated using linear and Cox-regression. The co-relative analysis was used to examine effects of shared familial confounding. We examined mediation and moderation of effect between ESR and IQ on psychosis risk. Results: Baseline IQ was associated with subsequent risk of schizophrenia (adjusted HR per 1-point increase in IQ = 0.961; 95% confidence interval (CI) 0.960–0.963) and ONAP (adjusted HR = 0.973; 95% CI 0.971–0.975). Higher ESR was associated with lower IQ in a dose-response fashion. High ESR was associated with increased risk for schizophrenia (adjusted HR = 1.14; 95% CI 1.01–1.28) and decreased risk for ONAP (adjusted HR = 0.85; 95% CI 0.74–0.96), although these effects were specific to one ESR band (7–10 mm/hr). Familial confounding explained ESR-IQ but not ESR-psychoses associations. IQ partly mediated the ESR-psychosis relationships. Conclusions: Lower IQ is associated with low-grade systemic inflammation and with an increased risk of schizophrenia and ONAP in adulthood. Low-grade inflammation may influence schizophrenia risk by affecting neurodevelopment. Future studies should explore the differential effects of inflammation on different types of psychosis. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Discussion 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. [ABSTRACT FROM AUTHOR]

Importance: Associations between childhood infection, IQ, and adult nonaffective 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., Objectives: To test the association of childhood infection with IQ and adult NAP, to find whether shared familial confounding explains the infection-NAP and IQ-NAP associations, and to examine whether IQ mediates and/or moderates the childhood infection-NAP association., Design, Setting, and Participants: Population-based longitudinal cohort study using linkage of Swedish national registers. The risk set included all Swedish men born between 1973 and 1992 and conscripted into the military until the end of 2010 (n = 771 698). We included 647 515 participants in the analysis., Measurement of Exposures: Hospitalization with any infection from birth to age 13 years., Main Outcomes and Measures: Hospitalization with an International Classification of Diseases diagnosis of NAP until the end of 2011. At conscription around age 18 years, IQ was assessed for all participants., Results: At the end of follow-up, the mean (SD) age of participants was 30.73 (5.3) years. Exposure to infections, particularly in early childhood, was associated with lower IQ (adjusted mean difference for infection at birth to age 1 year: -1.61; 95% CI, -1.74 to -1.47) and with increased risk of adult NAP (adjusted hazard ratio for infection at birth to age 1 year: 1.19; 95% CI, 1.06 to 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 to 0.978). The infection-NAP and IQ-NAP associations were similar in the general population and in full-sibling pairs discordant for exposure. The association between infection and NAP was both moderated (multiplicative, β = .006; SE = 0.002; P = .02 and additive, β = .008; SE = 0.002; P = .001) and mediated (β = .028; SE = 0.002; P < .001) by IQ. Childhood infection had a greater association with 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 and may be causal. Lower premorbid IQ in individuals with psychosis arises from unique environmental factors, such as early-childhood infection. Early-childhood infections may increase the risk of NAP by affecting neurodevelopment and by exaggerating the association of cognitive vulnerability with psychosis.