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Maternal C-Reactive Protein and Schizophrenia

To the Editor: In their article published in the September 2014 issue of the Journal, Sarah Canetta, Ph.D., et al. (1) report that increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio reported in the abstract=1.31; 95% confidence interval [CI]=1.10–1.56; adjusted odds ratio reported in the results=1.28; 95% CI=1.07–1.54). The authors interpret this finding from Finland as evidence that maternal inflammation plays a role in this disorder and claim that this inflammation may be due to infections during pregnancy.

Surprisingly, the authors do not mention the possibility that the increased C-reactive protein levels were caused by maternal smoking. Levels of C-reactive protein are increased in smokers and remain elevated up to 5 years after cessation (2, 3). This is important because schizophrenia patients are more likely to have a mother who smoked during pregnancy (4). Moreover, smoking during pregnancy is relatively common in Finland. An investigation in 1997 found high prevalence rates among single (30%) and less educated (25%) pregnant women (5). Thus, the increase in maternal C-reactive protein levels may be due, at least in part, to smoking. The same considerations apply to the association, reported by the same research group, between maternal C-reactive protein and autism (6).

Finally, it is worth remembering that the results of studies on the relationship between prenatal infection and schizophrenia are not entirely consistent. Birth during the 9-month period after the 1957 influenza pandemic, which produced infection rates of about 50%, was not a risk factor for schizophrenia (7).

From the Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, the Netherlands; and the Department of Psychosis Studies, King’s College London, King’s Health Partners, London.

The authors report no financial relationships with commercial interests.

References

1 Canetta S, Sourander A, Surcel HM, et al.: Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am J Psychiatry 2014; 171:960–968LinkGoogle Scholar

2 Bazzano LA, He J, Muntner P, et al.: Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann Intern Med 2003; 138:891–897Crossref, MedlineGoogle Scholar

3 Hastie CE, Haw S, Pell JP: Impact of smoking cessation and lifetime exposure on C-reactive protein. Nicotine Tob Res 2008; 10:637–642Crossref, MedlineGoogle Scholar

4 Stathopoulou A, Beratis IN, Beratis S: Prenatal tobacco smoke exposure, risk of schizophrenia, and severity of positive/negative symptoms. Schizophr Res 2013; 148:105–110Crossref, MedlineGoogle Scholar

5 Jaakkola N, Jaakkola MS, Gissler M, et al.: Smoking during pregnancy in Finland: determinants and trends, 1987–1997. Am J Public Health 2001; 91:284–286Crossref, MedlineGoogle Scholar

6 Brown AS, Sourander A, Hinkka-Yli-Salomäki S, et al.: Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry 2014; 19:259–264Crossref, MedlineGoogle Scholar

7 Selten JP, Frissen A, Lensvelt-Mulders G, et al.: Schizophrenia and 1957 pandemic of influenza: meta-analysis. Schizophr Bull 2010; 36:219–228Crossref, MedlineGoogle Scholar