FROM BRAIN, BEHAVIOR, AND IMMUNITY
Increases in inflammatory markers during acute psychosis suggest that higher C-reactive protein levels in adolescence may play an important role in subsequent schizophrenia by age 27, but more study is needed, results from a longitudinal study suggest.
“Inflammatory pathways may offer important new prevention and intervention targets for schizophrenia,” wrote Stephen A. Metcalf of the University of Cambridge (England) and his coauthors, most of whom are based in Finland ( Brain Behav Immun. 2017 Jan;59:253-9 ).
The birth cohort consisted of 99% of the live births in two northern Finland provinces between July 1985 and June 1986. Investigators studied 6,362 individuals within the cohort who had gone on to have their blood sampled at age 15 or 16 years and measured for levels of serum C-reactive protein (CRP).
Increased levels of CRP are associated with antipsychotic-naive first-episode psychosis and acute psychotic relapse. However, “it is difficult to ascertain the direction of association between inflammation and schizophrenia from cross-sectional data. Longitudinal studies of inflammatory markers and subsequent psychotic illness are scarce but are necessary to establish whether the increase in circulating inflammatory markers is a cause or consequence of illness,” wrote Mr. Metcalf and his coauthors.
The investigators searched Finnish hospital records for cases and ICD-10 diagnoses of nonaffective psychosis, including schizophrenia, for the years 1994 to 2012 for CRP-measured members of the birth cohort, spanning ages 8-27 years. With the records collected, they sorted the participants for analysis into the following three groups: schizophrenia (n = 22), nonschizophrenia nonaffective psychosis (n = 66), and no psychosis (n = 6,274).
“The adjusted [odds ratio] for schizophrenia by age 27 years for each standard deviation increase in CRP levels at age 15/16 years was 1.25 (95% confidence interval, 1.07-1.46), which was consistent with a linear, dose-response relationship (P = 0.23),” Mr. Metcalf and his coauthors wrote. Participants with high levels of CRP at baseline (greater than 3 mg/L), compared with low levels (less than 1 mg/L), were more likely to develop schizophrenia (adjusted OR, 4.25; 95% CI, 1.30-13.93).
The investigators adjusted their regression models for age, sex, body mass index, maternal education, smoking, and alcohol use. “To exclude reverse causality (i.e., schizophrenia leading to elevated CRP), we repeated the analyses after removing participants who had developed schizophrenia within one year of CRP assay.”
The findings build on those from a longitudinal study in Denmark on increased risks for schizophrenia associated with higher CRP levels ( Schizophr Bull. 2014 Sep;40[5]:1117-27 ). The authors cautioned that the current findings must be replicated elsewhere.
The authors disclosed several individual funding sources, but none played a role in the study.
