Summary: New research suggests children conceived after less than three years of parental sexual contact may face a slightly higher risk of developing schizophrenia.
Source: Mount Sinai Hospital
Overview: Researchers at the Icahn School of Medicine at Mount Sinai report that offspring born to couples who had been sexually involved for under three years prior to conception show a modestly increased risk of schizophrenia. The study was published April 23 in the journal Schizophrenia Research.
Schizophrenia is a severe, chronic psychiatric disorder that impairs thought, perception, emotion and behavior. Symptoms can include hallucinations, delusions, disorganized thinking, depressive features, and cognitive deficits. It is well established that schizophrenia arises from a complex interplay of genetic vulnerability and environmental exposures—such as prenatal infections, maternal malnutrition, birth complications, and psychosocial stressors—that together influence the likelihood that the disorder will develop.
Previous obstetric research has linked preeclampsia, a common pregnancy complication characterized by placental inflammation and maternal immune activation, with developmental changes in offspring that increase schizophrenia risk by two- to four-fold. Other studies indicate that prolonged vaginal exposure to a future father’s sperm before conception may reduce maternal immune intolerance to paternal antigens, lowering the risk of preeclampsia.
“We hypothesized that maternal immune intolerance to the father’s antigens could be a pathway linking short durations of preconception sexual contact to higher risk for schizophrenia,” said Dolores Malaspina, MD, MS, MPH, Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience at the Icahn School of Medicine at Mount Sinai and first author of the paper. “Our analysis shows that children born to parents married for less than three years carry a small but statistically significant increase in schizophrenia risk, independent of parental psychiatric history and paternal age.”
Earlier work by Dr. Malaspina found an association between short marriages and greater schizophrenia risk in offspring, with preeclampsia proposed as a possible mediator. That original study, however, did not fully separate the effects of parental psychiatric illness or the father’s age at marriage—factors that could reflect inherited vulnerability.
In the current study, the team disentangled interrelated variables including paternal age, father’s age at marriage, parental psychiatric diagnoses, and duration of marriage (used as a proxy for preconception sexual exposure). The researchers analyzed data on more than 90,000 children drawn from the Jerusalem Perinatal Cohort Schizophrenia Study (JPSS), a prospective, population-based birth cohort that recorded births in a defined area of Jerusalem from 1964 to 1976.
Key findings: children born to parents married for less than two years (approximately one year of preconception sexual contact) had about a 50 percent higher risk of schizophrenia compared with those born to parents with long marriages. Those whose parents had been married two to four years had roughly a 30 percent increased risk. Conversely, longer durations of marriage were associated with lower risk: every additional five years of marriage predicted about a 14 percent reduction in schizophrenia risk.
Because nearly all births in the JPSS cohort (97 percent) were to married couples, and out-of-wedlock births were uncommon in Israel at the time, duration of marriage serves as a plausible lower-bound estimate of the length of maternal vaginal exposure to the father’s sperm for this cohort, even though it is an imperfect proxy in many modern populations.
Dr. Malaspina notes that these results align with obstetric literature showing that shorter preconception sexual contact increases preeclampsia risk, and with recent genetic findings that implicate placental gene expression in schizophrenia susceptibility. “Prenatal immune activation from conditions like preeclampsia could create lasting inflammatory vulnerabilities in both mother and fetus, raising the long-term risk for psychiatric and metabolic disorders,” she said.
The research team is continuing to investigate whether short duration of preconception sexual contact is associated with other psychiatric or metabolic outcomes in offspring.
Collaborators on the study include investigators from New York University, University of Miami, Montefiore Medical Center, Columbia University, Hebrew University of Jerusalem, University Hospital Frankfurt, and Pluristem Therapeutics. Funding was provided by the National Institutes of Health and the G. Harold and Leila Y. Mathers Charitable Foundation.
Source:
Mount Sinai Hospital
Media Contact:
Elizabeth Dowling – Mount Sinai Hospital
Image Source:
Public domain
Original Research: Closed access. Article: “Short duration of marriage at conception as an independent risk factor for schizophrenia” — Dolores Malaspina et al., published in Schizophrenia Research. DOI: 10.1016/j.schres.2019.03.001
Abstract (summary): Short duration of marriage (DoM) is a known risk factor for preeclampsia and has been associated with schizophrenia risk. This analysis evaluated whether DoM independently predicts schizophrenia after accounting for parental psychiatric history and parental ages. Using Cox proportional hazards models in 90,079 offspring from the Jerusalem birth cohort (1964–1976), researchers found that each additional five years of DoM reduced schizophrenia risk. The greatest increased risk occurred when DoM was less than two years. These effects were independent of parental psychiatric diagnoses and paternal age. The findings suggest that brief preconception sexual exposure may contribute to prenatal immune pathways relevant to schizophrenia and merit further study.