Blomström Å, Gardner R M, Dalman C, Yolken R H, Karlsson H
Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transl Psychiatry. 2015 Feb 3;5(2):e502. doi: 10.1038/tp.2014.142.
Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975-1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1-4.0) or cytomegalovirus (1.7, 0.9-3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal-fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders.
虽然孕期初次感染弓形虫或疱疹病毒是公认的致畸原，但母体慢性感染这些病原体被认为严重程度要低得多。然而，这种慢性感染与后代的神经精神障碍有关。孕期接触这些病原体的后代患非情感性精神病（包括精神分裂症）的风险尚未完全明确。我们使用了来自199例非情感性精神病患者和525例匹配对照（出生于1975年至1985年）的新生儿干血样本数据。我们检测了针对弓形虫、巨细胞病毒以及1型和2型单纯疱疹病毒的免疫球蛋白G抗体，以及九种急性期蛋白（APP）的水平。我们评估了母体抗体与新生儿APP之间在非情感性精神病风险方面的相互作用。在对照组中，母体接触弓形虫或巨细胞病毒，但不接触其他疱疹病毒，与新生儿APP水平显著升高有关。在病例组中，母体接触这些病原体均未与APP的任何显著变化相关。我们仅在APP水平较低的新生儿中观察到，母体感染弓形虫（比值比2.1，95%置信区间1.1 - 4.0）或巨细胞病毒（1.7，0.9 - 3.3）与非情感性精神病的相对风险增加有关。这些发现表明，母体慢性感染弓形虫或巨细胞病毒会影响新生儿的先天免疫标志物。胎儿免疫反应不足与母体慢性感染相结合可能会增加后续患精神病的风险。对母婴免疫相互作用的更深入了解最终可能会带来针对神经精神障碍的预防策略。
