Abstract
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. 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. 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. 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.
Highlights
The neurodevelopmental hypothesis of schizophrenia posits that abnormal neurodevelopment contributes to the pathogenesis of the illness (Murray & Lewis, 1987; Weinberger, 1987)
With each one-point increase in IQ, risk decreased for schizophrenia, and for other non-affective psychoses (ONAP)
We showed that lower IQ is robustly associated with subsequent diagnoses of schizophrenia and ONAP
Summary
The neurodevelopmental hypothesis of schizophrenia posits that abnormal neurodevelopment contributes to the pathogenesis of the illness (Murray & Lewis, 1987; Weinberger, 1987) This hypothesis is supported by population-based longitudinal studies showing an association of schizophrenia and other non-affective psychoses (ONAP) with lower IQ during childhood/ premorbid period (Jones et al 1994; Crow et al 1995; David et al 1997; Davidson et al 1999; Cannon et al 2000, 2002; Zammit et al 2004; Reichenberg et al 2005; Kendler et al 2015). 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. Future studies should explore the differential effects of inflammation on different types of psychosis
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