Mother's herpes virus infection associated with schizophrenia in her offspring, Hopkins researcher finds

November 13, 2001

Scientists at Johns Hopkins Children's Center and six other research centers have found that mothers who have had a herpes simplex virus type 2 (HSV-2) infection at the time of birth are more likely to give birth to children who develop schizophrenia or other psychotic disorders. HSV-2 is a sexually transmitted disease that differs from its common, cold sore-causing cousin, HSV-1.

Based on stored blood samples and medical records dating as far back as the late 1950s, the correlative study in this month's Archives of General Psychiatry is the first to compare direct laboratory evidence of specific maternal infections with the development of psychosis in children.

"The evidence shows some association of maternal herpes simplex 2 virus with schizophrenia later in life," says Children's Center neurovirologist Robert Yolken, M.D., a coauthor of the study. "However, whether the herpes infection is a direct cause or just a factor is still unknown."

Researchers drew their subjects from the Providence, Rhode Island group of the Collaborative Perinatal Project (CPP), a large-scale, nationwide study that monitored 55,000 pregnancies at 12 study sites in the United States between 1959 and 1966. The CPP also evaluated infants for physical and mental development during the first seven years of life and stored blood samples from mothers for later analysis.

Of the 3,804 surviving offspring of 3,078 pregnant women from the Providence group, 27 children were diagnosed with schizophrenia or another psychotic disorder. Fifty-four other mothers and children without psychotic disorders from the Providence group were studied as a control group. The psychological health of children in the study was assessed by medical record analysis and telephone interviews. None of the offspring in the case group had experienced encephalitis or other major neurological abnormalities at birth.

The researchers determined maternal infection by the presence of elevated levels of antibodies to HSV-2. Antibodies to other infectious agents, including Chlamydia trachomatis (chlamydia), Toxoplasma gondii (toxoplasmosis), rubellavirus (rubella), cytomegalovirus (viral pneumonia), the human papilloma virus (genital warts), and HSV-1 (cold sores) were equally low in the mothers of both psychotic and non-psychotic children. Because antibodies to other sexually transmitted diseases were not different between the groups, Yolken says sexual activity of the mother is not, by itself, a predictive factor for the development of psychosis in their offspring.

Of the two major herpes simplex virus types, HSV-1 is extremely pervasive in the human population and does not require sexual contact to be transmitted. HSV-2 is rarer and more dangerous, and is typically transmitted sexually. The replication of both viruses can be countered by antiviral medications.
Stephen Buka, Sc.D., and Ming Tsuang, M.D., Ph.D., of Harvard's School of Public Health and School of Medicine and the Harvard Institute of Psychiatric Epidemiology and Genetics; E. Fuller Torrey, M.D., of the Stanley Research Laboratory; Mark Klebanoff, M.D., of the National Institute of Child Health and Human Development; and David Bernstein, M.D., of the Children's Hospital Medical Center in Cincinnati also contributed to the study. The Stanley Foundation funded the study with additional support from the National Institute of Mental Health.

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