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

Am J Psychiatry. 2014 Sep;171(9):960-8. doi: 10.1176/appi.ajp.2014.13121579.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Specimen Banks
  • C-Reactive Protein / analysis*
  • Case-Control Studies
  • Cohort Studies
  • Confidence Intervals
  • Female
  • Finland / epidemiology
  • Humans
  • Inflammation* / blood
  • Inflammation* / epidemiology
  • Male
  • Odds Ratio
  • Pregnancy
  • Pregnancy Proteins / blood
  • Prenatal Exposure Delayed Effects* / blood
  • Prenatal Exposure Delayed Effects* / epidemiology
  • Psychopathology
  • Risk Assessment
  • Risk Factors
  • Schizophrenia* / epidemiology
  • Schizophrenia* / etiology


  • Pregnancy Proteins
  • C-Reactive Protein