Exposure to Mother’s Heightened Immune Response in Womb May Increase Schizophrenia Risk

Exposure to a mother’s heightened immune response early in pregnancy may increase an individual’s risk of developing schizophrenia, suggests a study in Lancet Psychiatry.

“We found that higher concentrations of proinflammatory cytokines [TNFα, IL-1β, and IL-6] in specifically the first half of pregnancy were associated with a risk for psychosis among offspring, implicating an earlier timepoint in gestation than previously understood,” wrote Dana Allswede, M.S., and Tyrone Cannon, Ph.D., of Yale University and colleagues. “These three cytokines are potent proinflammatory proteins that have a critical role in the initial response to infection and in initiating and sustaining inflammatory responses.”

The findings were based on data collected for the National Collaborative Perinatal Project (NCPP)—a large-scale prospective longitudinal study. As part of this study, pregnant women from across the United States provided blood samples at prenatal visits and birth from 1958 to 1965.

Allswede, Cannon, and colleagues focused on the women and offspring in the Philadelphia cohort of NCPP, which included 9,236 surviving offspring of 6,753 pregnant women. The researchers examined medical records to determine whether the offspring developed psychotic disorders by adulthood. They also analyzed the concentrations of the following cytokines in the maternal blood samples: TNFα, IL-1β, IL-5, IL-6, IL-8, IL-10, and IL-17a.

The final sample included 90 offspring who later developed psychosis, 79 siblings who did not have psychotic disorder, and 273 matched controls who did not have psychosis. The researchers found that concentrations of proinflammatory cytokines TNFα, IL-1β, and IL-6 were significantly higher in the maternal blood samples of the offspring who later developed psychosis compared with maternal blood samples of the matched controls. “These differences were greatest in the first half of pregnancy …, with no difference observed during the second half of pregnancy,” the authors noted. Siblings and the matched controls did not significantly differ for any of the cytokines.

“Understanding which environmental factors interact with maternal inflammation to increase the risk for psychotic conditions in the offspring, and the pathways through which they act, might provide a framework for early intervention (whether at the maternal, paternal, or childhood level) and build momentum for a much-needed preventive approach to neuropsychiatric disorders,” wrote Bruno Agustini, M.D., Ph.D., and Michael Berk, Ph.D., M.B.B.Ch., of Deakin University in an accompanying editorial.

For related information, see the American Journal of Psychiatry article “Maternal Bacterial Infection During Pregnancy and Offspring Risk of Psychotic Disorders: Variation by Severity of Infection and Offspring Sex.”

(Image: pio3/Shutterstock)

Follow Psychiatric News on Twitter!

And check out the new Psychiatric News Brief on Alexa-enabled devices.

Calculator Shows Promise in Predicting Risk for Conversion to Psychosis

Although considerable progress has been made in determining risk factors for psychosis in recent decades, mental health professionals currently lack a widely available tool for calculating a precise estimate of risk for patients seeking help. Two studies published today in AJP in Advance suggest researchers have developed a risk calculator for the individualized prediction of a psychotic disorder over a two-year period.

In the first study, researchers led by Tyrone Cannon, Ph.D., a professor of psychology and psychiatry at Yale University, described how they examined eight criteria to evaluate the prediction of psychotic disorder in 596 participants (mean age 18.5 years) over a two-year period in the North American Prodrome Longitudinal Study (NAPLS-2).

“Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis,” Cannon and colleagues wrote. However, other variables—stressful life events, trauma, or a family history of schizophrenia—did not predict conversion to psychosis, they said. The overall model accuracy rate was 71%—which the authors noted is “in the range of values for established calculators currently in use for cardiovascular disease and cancer recurrence risk, which range from 0.58 to 0.81.”

“This prediction tool represents a potential breakthrough for early intervention in psychiatry. However, as with any predictive analytic model, its performance must be validated in samples of clinical high-risk patients collected independently of NAPLS-2,” Ricardo Carrión, Ph.D., an assistant professor of psychiatry at Hofstra Northwell School of Medicine in Hempstead, N.Y., and colleagues wrote in a companion article.

Carrión’s team evaluated the performance of the NAPLS-2 risk calculator in an external, independent sample of individuals (aged 12 to 25) at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP). The overall model accuracy rate was 79% in the EDIPPP sample. 

“Although further replication is needed, at present the risk calculator appears to have considerable potential for determining the probability that an individual will develop psychosis, and it may provide a foundation for the personalized treatment of clinical high-risk individuals,” Carrión and colleagues wrote.

For more in Psychiatric News about the Early Detection and Intervention for the Prevention of Psychosis Program, see “Early Intervention Trial in Youth at Risk for Psychosis Shows Improved Symptoms.”

(Image: iStock/monkeybusinessimages)