Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort

Abstract

Objective: The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank.

Method: A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens.

Results: Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status.

Conclusions: This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

Figure 1

Distribution of CRP values for cases and controls. The graph depicts the frequency of cases and controls with CRP values (mg/L) in the given intervals.

Figure 2

Median CRP values for cases and controls by gestational week of the blood draw. The graph shows the median CRP value (mg/L) for cases and controls with maternal serum obtained in the indicated range of gestational weeks.