Maternal Infection, Later Childhood Infection Linked to Psychosis in Offspring

Maternal psychiatric disorders and maternal infection during pregnancy appear to act synergistically with exposure to later childhood infection in offspring by increasing the risk of psychosis in those offspring, according to a report in the January Schizophrenia Bulletin.

The study from a large Swedish birth cohort found that maternal infection alone during pregnancy was not statistically significantly linked to psychosis in offspring. But among mothers with a history of psychiatric illness, infection during pregnancy appeared to contribute to the risk of later childhood infections in offspring and to higher risk of psychosis in those offspring, according to the report.

“A genetic predisposition to psychosis in conjunction with one or more environmental insults has been proposed in the etiology of psychosis,” wrote researchers from the Karolinska Institute in Stockholm. “We found evidence for synergism between maternal psychiatric disorder (a proxy marker of genetic predisposition in the mother as well as the child) and infection during pregnancy on psychosis risk in the offspring, which is in agreement with previous observations. … Importantly, exposure to maternal infection did not appear to interact with paternal psychiatric disorder (a proxy for genetic predisposition in the father as well as the child). … These results indicate an effect of acute infections during pregnancy specific to vulnerable mothers on the risk for the offspring to later develop nonaffective psychosis.”

The study drew on data from several national registries uniquely accessible in Sweden. These include Psychiatry Sweden, which links several health and population registers created for studies of the etiology of psychiatric disorders; the National Patient Register, which was used for identification of infection and nonaffective psychoses and includes virtually all inpatient care in Sweden since 1973 and psychiatric outpatient visits since 2001; and the Medical Birth Register, which includes data from the prenatal, delivery, and neonatal periods from almost all deliveries in Sweden.

The researchers used statistical analysis to examine several different possible associations with psychosis in offspring whose parents did or did not have psychiatric illness—the link between exposure to maternal infection during pregnancy and psychosis, between exposure to maternal infection and later childhood infection, and between combined exposure to maternal infection during pregnancy and later childhood infection and risk for psychosis.

In the total population, there was a small but significantly increased risk of developing nonaffective psychosis among children whose mothers were hospitalized for infection during pregnancy, but this association disappeared when adjusted for confounding variables. In contrast, among individuals whose parents were diagnosed with a psychiatric disorder, exposure to maternal infection during pregnancy was significantly associated with psychosis; further, there was an interaction between maternal infection during pregnancy and childhood infection in terms of the risk of nonaffective psychosis.

Research interest in a possible link between schizophrenia and viruses and infection, once strictly outside the mainstream, has become an important and seriously regarded line of inquiry. The January issue of Schizophenia Bulletin also has two other articles studying the relationship between infection and schizophrenia.

The authors of the current paper noted that many of the genetic loci that so far have been associated with schizophrenia are located within the major histocompatibility (MHC) region on chromosome 6, a region dense with genes linked to both immunity and brain development.

“Interestingly, genetic risk for schizophrenia, both within and outside the MHC region, appears to overlap with risk for other psychiatric diagnoses, which suggests that genetic variation in many regions, including the MHC region, may explain some of the interaction between maternal psychiatric disease and infection.”

They added that brain development proceeds through early adulthood and is therefore potentially continuously vulnerable to disruptive influences that may be more likely to occur in individuals with immune deficits.

“Here we observed that individuals whose mothers were exposed to infections before and, particularly, during pregnancy were themselves more likely to be hospitalized for infections during childhood,” they stated. “Importantly, exposure to maternal infection during … pregnancy and to a subsequent childhood infection acted synergistically on future psychosis risk. These observations indicate that maternal infection during pregnancy can modify not only the future risk of the offspring to be hospitalized for infection, but also the long-term outcomes of such infections.” ■

“Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder—A Swedish Cohort Study of Nearly 2 Million Individuals” can be accessed here.