The Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, 1105 Blalock, Baltimore, MD 21287-4933, USA.
Microbes Infect. 2009 Nov;11(13):1011-8. doi: 10.1016/j.micinf.2009.07.007. Epub 2009 Jul 26.
Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring. Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens, GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type capital I, Ukrainian infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio=1.94; 95% confidence interval=1.08-3.46; p=0.03). The risk was particularly elevated for affective psychoses (OR=5.24; 95% CI=1.67-16.5; p=0.005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring. These findings suggest an influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis.
先前的研究表明，怀孕期间母体对弓形虫的抗体与成年后代精神分裂症和其他精神病的风险增加有关。最近，人们已经认识到，不同基因型的弓形虫具有不同的神经致病潜力。本研究的目的是探讨寄生虫基因型是否是疾病风险的一个因素。我们开发了一种酶联免疫吸附试验（ELISA），该试验使用针对三种克隆寄生虫谱系的多态多肽，这些多肽源自三种致密颗粒抗原，即 GRA5、GRA6 和 GRA7。我们使用该检测方法测量了来自 219 名孕妇的血清中的特定类型的抗体，这些孕妇的孩子在成年后患上了精神分裂症和情感性精神病，以及来自三个合作围产期项目队列的 618 名匹配的未受影响的对照母亲。我们发现，与匹配的未受影响的对照母亲相比，血清学模式与弓形虫 I 型、乌克兰感染一致的母亲的孩子患精神病的风险显著增加（比值比=1.94；95%置信区间=1.08-3.46；p=0.03）。情感性精神病的风险特别高（OR=5.24；95%CI=1.67-16.5；p=0.005）。相比之下，我们没有发现母体对其他基因型的抗体与后代患精神病的风险之间存在关联。这些发现表明寄生虫基因型对精神病风险增加有影响，并进一步支持弓形虫在精神病病因学中的实质性作用。
