University of Oulu

Stephen A. Metcalf, Peter B. Jones, Tanja Nordstrom, Markku Timonen, Pirjo Mäki, Jouko Miettunen, Erika Jääskeläinen, Marjo-Riitta Järvelin, Jan Stochl, Graham K. Murray, Juha Veijola, Golam M. Khandaker, Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study, Brain, Behavior, and Immunity, Volume 59, January 2017, Pages 253-259, ISSN 0889-1591, (

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

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Author: Metcalf, Stephen A.1; Jones, Peter B.1; Nordström, Tanja2,3;
Organizations: 1Department of Psychiatry, University of Cambridge, Cambridge, UK
2Center for Life-Course Health Research, University of Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
4Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Finland
5Department of Psychiatry, Oulu University Hospital, Finland
6Department of Psychiatry, Länsi-Pohja Healthcare District, Finland
7Department of Psychiatry, The Middle Ostrobothnia Central Hospital, Kiuru, Finland
8Mental Health Services, Joint Municipal Authority of Wellbeing in Raahe District, Finland
9Mental Health Services, Basic Health Care District of Kallio, Finland
10Visala Hospital, The Northern Ostrobothnia Hospital District, Finland
11Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London, UK
12Biocenter Oulu, P.O. Box 5000, Aapistie 5A, FI-90014, University of Oulu, Finland
13Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220 Oulu 90029 OYS, Finland
14Corresponding author at: Department of Psychiatry, University of Cambridge, Box 189, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Elsevier, 2017
Publish Date: 2017-03-24


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 27 years, 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 27 years for each standard deviation (SD) increase in CRP levels at age 15/16 years was 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 (>3 mg/L) compared with low (<1 mg/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.

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Series: Brain, behavior, and immunity
ISSN: 0889-1591
ISSN-E: 1090-2139
ISSN-L: 0889-1591
Volume: 59
Pages: 253 - 259
DOI: 10.1016/j.bbi.2016.09.008
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: 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.
Academy of Finland Grant Number: 124257
Detailed Information: 124257 (Academy of Finland Funding decision)
214273 (Academy of Finland Funding decision)
268336 (Academy of Finland Funding decision)
Dataset Reference: Supplementary data associated with this article can be found, in the online version, at
Copyright information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (