EMBARGOED UNTIL MAY 1, 2004 

STUDY OF ADULTS WITH SCHIZOPHRENIA POINT TO
ENVIRONMENTAL COMPONENT

Interleukin-8 (IL-8), one of a number of molecules called cytokines, which are critical for the body’s response to infection, was present at high levels in the second trimester of women whose children developed schizophrenia. The finding, published in the May issue of the American Journal of Psychiatry, is the latest implicating prenatal infection—in effect, the prenatal environment—in the development of schizophrenia.

Cytokines, particularly in elevated levels, have long been identified as key players in other brain disorders including cerebral palsy and autism. Alan Brown, MD, a research scientist at the New York State Psychiatric Institute and Associate Professor of Clinical Psychiatry at Columbia University Medical Center, led a group of scientists in analyzing blood serum of 59 pregnant mothers of subjects who later developed schizophrenia and related disorders and 105 mothers of comparison subjects without schizophrenia. Their goal was to determine whether second-trimester levels of four cytokines including IL-8, were higher in the mothers of children who later developed schizophrenia than in mothers of the comparison group.

Only IL-8 showed up in significantly higher quantities in the mothers of subjects with schizophrenia—nearly twice the levels of those found in mothers of the comparison group—during the second trimester. Three additional analyses were conducted and yielded the same results.

“These findings may help us better understand the way that abnormal brain development in utero contributes to the risk of schizophrenia later in life. If we can understand that better then this may help us identify, which receptors and neural circuits might be involved in the illness that can be targeted by medication. Once we can show these links between markers of infection and schizophrenia, then we can encourage healthcare providers including obstetricians and internists to move towards early screening for these infections,” said Dr. Brown. “But that is a very long way off and replication in independent samples is required.”

The researchers also noted that high levels of IL-8 may be indicative of “a non-infectious inflammatory process that contributes to schizophrenia risk. Elevated levels of IL-8 and other cytokines have also been demonstrated in several noninfectious conditions, including pre-eclampsia, preterm birth and obesity, each of which has been associated with schizophrenia and can adversely affect fetal development.”

Research subjects were drawn from a large cohort of individuals born in California between 1959 and 1967 and enrolled in the Kaiser Foundation Health Plan, which kept detailed, daily records of enrollees an drew and stored blood samples from virtually all of their mothers. Subjects were matched for date of birth and the number and timing of maternal blood samples during pregnancy. The investigators also adjusted for the effects of the mothers’ educational, ethnic and smoking status and found that they did not affect the results.

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