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


METHODS
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.
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Stephen A
SA
Metcalf
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Peter B
PB
Jones
Center for Life-Course Health Research, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland.
Tanja
T
Nordstrom
Center for Life-Course Health Research, University of Oulu, Finland.
Markku
M
Timonen
Center for Life-Course Health Research, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Finland; Department of Psychiatry, Länsi-Pohja Healthcare District, Finland; Department of Psychiatry, The Middle Ostrobothnia Central Hospital, Kiuru, Finland; Mental Health Services, Joint Municipal Authority of Wellbeing in Raahe District, Finland; Mental Health Services, Basic Health Care District of Kallio, Finland; Visala Hospital, The Northern Ostrobothnia Hospital District, Finland.
Pirjo
P
Mäki
Center for Life-Course Health Research, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland.
Jouko
J
Miettunen
Center for Life-Course Health Research, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland.
Erika
E
Jääskeläinen
Center for Life-Course Health Research, University of Oulu, Finland; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, UK; Biocenter Oulu, P.O. Box 5000, Aapistie 5A, FI-90014, University of Oulu, Finland; Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220 Oulu 90029 OYS, Finland.
Marjo-Riitta
MR
Järvelin
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Jan
J
Stochl
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Graham K
GK
Murray
Center for Life-Course Health Research, University of Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland.
Juha
J
Veijola
Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: gmk24@medschl.cam.ac.uk.
Golam M
GM
Khandaker
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D038801:International Classification of Diseases; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000453:epidemiology; D012042:Registries; D012306:Risk; D012559:Schizophrenia / Q000097:blood* / Q000453:epidemiology; D055815:Young Adult
D002097:C-Reactive Protein
Adolescent; Adult; C-reactive protein; Inflammatory markers; Longitudinal study; Psychotic disorders; Schizophrenia; Systemic inflammation