Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis

Abstract

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.

Figure 1

Participant flow, exclusions and losses.

Figure 2

Odds ratios (ORs) and 95% confidence intervals of non-affective psychosis or schizophrenia according to maternal T. gondii exposure status and levels of each acute phase protein (APP) (lowest 1/3 tertile, and highest 2/3 tertile) and APP score (below median and above median). tPA, tissue-type plasminogen activator.

Figure 3

Odds ratios (OR) and 95% confidence intervals of non-affective psychosis or schizophrenia according to maternal cytomegalovirus (CMV) exposure status and levels of each acute phase protein (APP) (lowest 1/3 tertile, and highest 2/3 tertile) and APP score (below median and above median).