Maternal inflammatory marker linked to children’s schizophrenia risk

The children of women who have elevated levels of the inflammatory marker C-reactive protein (CRP) during pregnancy have an increased risk of developing schizophrenia, research suggests.

For the study, researchers measured CRP in archived maternal serum samples from the mothers of 777 schizophrenia or schizoaffective disorder patients and 777 matched controls in the Finnish Prenatal Study of Schizophrenia cohort. The serum samples were drawn during the first and second trimesters, giving an indication of prenatal conditions, rather than conditions at the time of delivery.

“Given the design advantages, this study provides the most robust evidence to date that maternal inflammation during pregnancy is related to the risk of schizophrenia in offspring and is consistent with many preclinical studies that have suggested a causal association”, say study author Alan Brown (Columbia University Medical Center, New York, USA) and team.

They found that the offspring of mothers with clinically abnormal CRP levels (≥10 mg/L) were 1.58-fold more likely to have schizophrenia than those whose mothers had lower levels, after accounting for confounders including maternal age, parental psychiatric disorders and the gestational week of the blood draw.

These levels of CRP may indicate recent infection or an active inflammatory process, making the finding consistent with previously reported links between maternal infection and schizophrenia in offspring, say Brown et al.

They say this could have “important implications for disease prevention, given that many standard approaches already exist to reduce the incidence of infections or lessen the severity of the inflammation that they produce.”

However, the team also found a significant association between CRP as a continuous variable and schizophrenia risk, with each 1 mg/L increase in CRP associated with a 28% increased risk of schizophrenia after accounting for confounding variables. This finding “may indicate that even mildly elevated levels, which may reflect a low-grade inflammatory process, are related to schizophrenia in offspring.”

The researchers note that previous findings in the same birth cohort also demonstrated a link between maternal CRP levels and autism in offspring. “It is intriguing to speculate that maternal inflammation during pregnancy may ‘prime’ the brain to broadly increase risk for the later development of different types of psychiatric syndromes”, they write in The American Journal of Psychiatry.

They conclude: “If replicated, these findings may have important implications for elaborating the role of immune system dysfunction in schizophrenia.”

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