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Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study.

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Metcalf, Stephen A 
Jones, Peter B 
Nordstrom, Tanja 
Timonen, Markku 
Mäki, Pirjo 


OBJECTIVE: Meta-analyses of cross-sectional studies confirm an increase in circulating inflammatory markers during acute psychosis. Longitudinal studies are scarce but are needed to understand whether elevated inflammatory markers are a cause or consequence of illness. We report a longitudinal study of serum C-reactive protein (CRP) in adolescence and subsequent risk of schizophrenia and related psychoses in adulthood in the Northern Finland Birth Cohort 1986. METHOD: Serum high-sensitivity CRP was measured at age 15/16 years in 6362 participants. ICD-10 diagnoses of schizophrenia and related psychoses were obtained from centralised hospital inpatient and outpatient registers up to age 27 years. Logistic regression calculated odds ratios (ORs) for psychotic outcomes associated with baseline CRP levels analysed as both continuous and categorical variables using American Heart Association criteria. Age, sex, body mass index, maternal education, smoking, and alcohol use were included as potential confounders. RESULTS: By age 27years, 88 cases of non-affective psychosis (1.38%), of which 22 were schizophrenia (0.35%), were identified. Adolescent CRP was associated with subsequent schizophrenia. The adjusted OR for schizophrenia by age 27yearsfor each standard deviation (SD) increase in CRP levels at age 15/16yearswas 1.25 (95% CI, 1.07-1.46), which was consistent with a linear, dose-response relationship (P-value for quadratic term 0.23). Using CRP as a categorical variable, those with high (>3mg/L) compared with low (<1mg/L) CRP levels at baseline were more likely to develop schizophrenia; adjusted OR 4.25 (95% CI, 1.30-13.93). There was some indication that higher CRP was associated with earlier onset of schizophrenia (rs=-0.40; P=0.07). CONCLUSIONS: A longitudinal association between adolescent CRP levels and adult schizophrenia diagnosis indicates a potentially important role of inflammation in the pathogenesis of the illness, although the findings, based on a small number of cases, need to be interpreted with caution and require replication in other samples.



Adolescent, Adult, C-reactive protein, Inflammatory markers, Longitudinal study, Psychotic disorders, Schizophrenia, Systemic inflammation, Adolescent, Adult, Age of Onset, C-Reactive Protein, Cohort Studies, Cross-Sectional Studies, Female, Finland, Humans, International Classification of Diseases, Longitudinal Studies, Male, Prospective Studies, Psychiatric Status Rating Scales, Psychotic Disorders, Registries, Risk, Schizophrenia, Young Adult

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Brain Behav Immun

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Elsevier BV
National Institute for Health Research (NIHR) (via Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Wellcome Trust (201486/Z/16/Z)
Academy of Medical Sciences (unknown)
Medical Research Council (G0701911)
Wellcome Trust (088869/Z/09/Z)
Wellcome Trust (095844/Z/11/Z)
Wellcome Trust (093875/Z/10/Z)
National Institute for Health and Care Research (RP-PG-0606-1335)
Medical Research Council (G0701911/1)
Dr. Khandaker 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). Prof. Jones acknowledges grant support from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0606-1335). Prof. Veijola was supported by the Academy of Finland (grants no. 124257, 212828, 214273). Prof. Mäki has been supported by the Signe and Ane Gyllenberg Foundation, Finland. Prof. Miettunen was supported by the Academy of Finland (grant no. 268336). Dr. Stochl was funded by the Medical Research Council (MR/K006665/1) and the NIHR Collaboration for Leadership in Applied Health Research & Care (CLAHRC) East of England.