Canetta Sarah, Sourander Andre, Surcel Heljä-Marja, Hinkka-Yli-Salomäki Susanna, Leiviskä Jaana, Kellendonk Christoph, McKeague Ian W, Brown Alan S
Am J Psychiatry. 2014 Sep;171(9):960-8. doi: 10.1176/appi.ajp.2014.13121579.
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.
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.
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.
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.
本研究的目的是在一个拥有大量血清生物样本库的全国性出生队列中,调查孕早期血清中检测的炎症生物标志物C反应蛋白与精神分裂症之间的关联。
采用芬兰精神分裂症产前研究队列中的巢式病例对照设计。共识别出777例有母亲血清可用于C反应蛋白检测的精神分裂症病例(精神分裂症,n = 630;分裂情感性障碍,n = 147),并在分析中与777名对照者进行匹配。使用来自存档母亲血清样本的乳胶免疫测定法评估母亲的C反应蛋白水平。
将母亲C反应蛋白水平作为连续变量分类,其升高与后代精神分裂症显著相关(调整后的优势比 = 1.31,95%置信区间 = 1.10 - 1.56)。在调整了潜在混杂因素后,这一发现仍然显著,这些混杂因素包括母亲和父母的精神疾病史、双胎/单胎出生、城市化程度、出生省份以及母亲的社会经济地位。
这一发现提供了迄今为止最有力的证据,表明母亲炎症可能在精神分裂症中起重要作用,这可能对确定精神分裂症及其他神经发育障碍的预防策略和致病机制具有启示意义。