Prenatal exposure to lead may be linked to the development of schizophrenia in young adulthood, according to a recent study. This report is one of the first prospective studies of a prenatal chemical exposure as a risk factor for an adult psychiatric disease.

Researchers at the Mailman School, Columbia University Medical Center (CUMC), and New York State Psychiatric Institute (NYSPI) analyzed second-trimester blood serum samples from a maternal cohort from Oakland, California, from 1959 to 1966, said Mark Opler, PhD, MPH, postdoctoral research fellow in the Department of Psychiatry at CUMC and first author of the study. The results were presented at the annual meeting of the American Association for the Advancement of Science and were published in the April issue of Environmental Health Perspectives.

TWICE AS LIKELY

The investigators compared levels of a biological marker of lead exposure, delta-aminolevulinic acid, and a diagnosis of schizophrenia. The study consisted of 44 patients diagnosed with schizophrenia and 75 controls; all were born at Kaiser Permanente Medical Care Plan clinics.

Individuals with elevated levels of prenatal delta-aminolevulinic acid were about twice as likely to receive a diagnosis of schizophrenia in young adulthood as those with lower levels, said Ezra Susser, MD, DrPH, Professor and Chair of Epidemiology at the Mailman School of Public Health and Head of Epidemiology of Brain Disorders at NYSPI. “The results of our study suggest that lead-induced prenatal damage to the developing brain may show itself decades following initial exposure to the substance,” said Dr. Susser.

Working with the hypothesis that prenatal lead exposures may be a risk factor for other adolescent and adult-onset outcomes, possibly psychiatric disorders, the researchers suspect that “schizophrenia is one plausible candidate because some of its premorbid features such as reduced attention, neurocognitive impairment, and diminished educational attainment strongly resemble the behavioral deficits associated with lead exposure.”

GET THE LEAD OUT

“Although blood lead levels in the United States have declined, lead exposure continues to be of great concern,” wrote the investigators. For more than two decades, there have been bans on both leaded gasoline and lead-based paint; nevertheless, it is estimated that 5% of children and infants still have high blood-lead levels, and in some areas that figure is estimated to be as high as 29%. Internationally, the researchers pointed out, lead exposure remains a concern because use of leaded gasoline continues in many parts of the world.

They postulated that both direct and indirect mechanisms should be considered regarding lead exposure during development. Direct mechanisms could involve physical interactions between lead and “the developing nervous system, interfering with growth, differentiation, or structural development.” Indirect mechanisms might include effects of lead that are not specific to the central nervous system, such as renal damage, or interactions with nutrient absorption and distribution, they suggested. “One specific indirect mechanism that must be considered is the potential toxicity of delta-aminolevulinic acid.” A known neurotoxin, elevated levels of the acid are associated with psychosis in adults. “It is possible that delta-aminolevulinic acid itself elevates the risk of schizophrenia spectrum disorders, independently or as a consequence of lead exposure,” they submitted.

The investigators are working on a follow-up study to validate their results in a larger sample. They believe more research is needed due to the fact that their initial results, when adjusted for confounding factors associated with both lead exposure and schizophrenia—such as parental age, socioeconomic status, maternal smoking, or alcohol use—only approached statistical significance, which makes it difficult to draw definitive conclusions.

—Heidi W. Moore

Suggested Reading
Opler MG, Brown AS, Graziano J, et al. Prenatal lead exposure, delta-aminolevulinic acid, and schizophrenia. Environ Health Perspect. 2004;112:548-552.

Return to table of contents