The children of mothers exposed to genital/reproductive infections in the
months surrounding conception have an increased risk of developing
schizophrenia, according to a new report from the Prenatal Determinants of
Schizophrenia (PDS) study.
The study requires replication but adds to accumulating evidence that the
origins of schizophrenia may lie in events occurring during gestation. It
appears in the May American Journal of Psychiatry.
The PDS study has already explored associations between prenatal influenza,
toxoplasmosis, and rubella and later incidence of schizophrenia.
"More important than any individual study is the gestalt that comes
out of this line of research," Mark Opler, Ph.D., a research scientist
in the Department of Epidemiology at Columbia University, told Psychiatric
News. Opler has conducted studies of prenatal lead exposure as a possible
cause of schizophrenia and has collaborated with some of the co-authors of the
current study.
"There is emerging a strong body of evidence showing that
perturbation of some kind definitely affects the risk on the incidence of
disorders in midlife," he said.
Vicki Babulas, M.P.H., and colleagues examined data from the Child Health
and Development Study, which enrolled 7,794 women from the Kaiser Permanente
Medical Care Plan in Alameda, Calif., between 1959 and 1966. Researchers such
as Jacob Yerushalmy, founder of the Child Health and Development Study, took a
long view and set up the organizations and systems to do studies decades into
the future.
Checking obstetric and medical records, Babulas and colleagues noted
diagnoses of endometritis, cervicitis, pelvic inflammatory disease, vaginitis,
syphilis, condylomata, or "venereal disease" in the women they
studied. They diagnosed 71 cases of schizophrenia spectrum disorder, either
using the Diagnostic Interview for Genetic Studies (44) and/or chart review
(27).
Children of women exposed to genital or reproductive infections during
periconception (from 30 days before the last menstrual period to 30 days after
the last period) had a five times greater chance of developing schizophrenia
than unexposed control children. Results were adjusted for maternal race,
education, age, and mental illness.
The timing of infection appeared significant. Exposure in the first
trimester after the periconceptual period or in the second or third trimester
produced no such association, wrote Babulas and colleagues.
"It's not just the exposure, but the timing of the exposure,"
said Opler. Infections might have different effects if they occur at different
times in the pregnancy, he said. If researchers knew the effects that
biological agents had at specific stages of development, they could know what
systems were likely to be affected at critical points and eventually link
etiology with symptoms.
Babulas and colleagues suggested that the effects on the fetus of such
infections are biologically plausible. Pathogens for genital or reproductive
infections might ascend from the perineum, vagina, or cervix to infect the
fetus directly, they wrote. "Alternatively, the pathogenic organism may
be transmitted by traversing the placental tissues, gaining access to the
fetal bloodstream, and crossing into the developing brain."
The study is limited by the low numbers of cases exposed to
genital/reproductive infections in the womb (five), a lack of serological
confirmation of infection, and a definition of infection that includes a
number of different microbes. Like previous PDS reports, this study used
maternal serum immune markers, not data from inside the fetal compartment.
Nonetheless, the study is bolstered by use of prospective diagnosis and
documentation of the mothers' infections and by face-to-face assessments of
schizophrenia spectrum disorder.
"We're still in the early stages of studying these effects, but in 10
years [the research has] produced groundbreaking results," said
Opler.
"Prenatal Exposure to Maternal Genital and Reproductive
Infections and Adult Schizophrenia" is posted at<http://ajp.psychiatryonline.org/cgi/content/full/163/5/927>.▪