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dc.contributor.authorKhandaker, Golamen
dc.contributor.authorKappelmann, Nilsen
dc.contributor.authorStochl, Janen
dc.contributor.authorJones, Peteren
dc.description.abstractBackground 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 pathogenesis of psychosis. Methods Population-based data on ESR and IQ from 638213 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. 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% 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 (7-10mm/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 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.
dc.description.sponsorshipThe authors have no financial interests to disclose with regard to the content of this study. PBJ received an honorarium, that he donated to his department, from Roche (UK) for taking part in an advisory board to advise on education about schizophrenia for psychiatrists. GMK is supported by an Intermediate Clinical Fellowship from the Wellcome Trust (201486/Z/16/Z) and a Clinical Lecturer Starter Grant from the Academy of Medical Sciences, UK (grant no. 80354). PBJ acknowledges grant support from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0616-20003, Cambridge Biomedical Research Centre and CLAHRC East of England). HK acknowledges support from the Stanley Medical Research Institute. The funding bodies had no role in design, conduct, analysis or reporting of this study.
dc.publisherCambridge University Press
dc.rightsAttribution 4.0 International*
dc.titleSystemic Inflammation and Intelligence in Early Adulthood and Subsequent Risk of Schizophrenia and Other Non-Affective Psychoses: A Longitudinal Cohort and Co-Relative Studyen
prism.publicationNamePsychological Medicineen
dc.contributor.orcidKhandaker, Golam [0000-0002-4935-9220]
dc.contributor.orcidStochl, Jan [0000-0002-9693-9930]
dc.contributor.orcidJones, Peter [0000-0002-0387-880X]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idWellcome Trust (201486/Z/16/Z)
pubs.funder-project-idWellcome Trust (088869/Z/09/Z)
pubs.funder-project-idWellcome Trust (095844/Z/11/Z)
pubs.funder-project-idNational Institute for Health Research (NIHR) (via Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (RP PG-0616-20003)
cam.orpheus.successThu Jan 30 12:59:27 GMT 2020 - The item has an open VoR version.*

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International