Academic journal article Environmental Health Perspectives

Prenatal Exposure to Lead, [Delta]-Aminolevulinic Acid, and Schizophrenia: Further Evidence

Academic journal article Environmental Health Perspectives

Prenatal Exposure to Lead, [Delta]-Aminolevulinic Acid, and Schizophrenia: Further Evidence

Article excerpt

BACKGROUND: A previously conducted study of prenatal lead exposure and schizophrenia using [delta]-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959-1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life.

OBJECTIVES: In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959-1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort.

METHODS: We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education.

RESULTS: The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 [mu]g/dL of blood Pb was 1.92 (95% confidence interval, 1.05-3.87; p = 0.03).

CONCLUSION: Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders.

KEY WORDS: [delta]-aminolevulinic acid, developmental, lead, Pb, prenatal, prospective, psychosis, schizophrenia. Environ Health Perspect 116:1586-1590 (2008). doi:10.1289/ehp. 10464 available via http://dx.doi.org/[Online 30 July 2008]

A growing body of evidence supports the hypothesis that exposures that damage or disrupt the developing central nervous system are associated with schizophrenia and related disorders (McGrath and Murray 2003). Associations for some prenatal exposures have low been replicated--for example, nutritional deprivation (St. Clair et al. 2005; Susser et al. 1996). Exposure to potentially neurotoxic metals has not been carefully examined to date. In an earlier study, we measured a marker of second-trimester exposure to lead in prospectively collected serum samples from a birth cohort (Opler et al. 2004). The risk for schizophrenia spectrum disorders in adulthood was shown to be approximately doubled in subjects with maternal blood Pb levels BPb) > 15 ug/dL [indicated by elevated levels of [delta]-aminolevulinic acid ([delta]-ALA)] during the second trimester, although the sample was too small to draw definitive conclusions and the results failed to reach statistical significance.

There are reasons to suspect that chemical agents in general, and particularly those associated with industrialization, may increase the risk of schizophrenia. Pb is a widely recognized developmental toxicant, leading to cognitive, behavioral, and physical impairments. Prospective birth cohorts in various parts of the world are consistent in finding that increased Pb exposure during development is associated with decrements in intellectual function up to 10 years of age [for a review, see Lanphear et al. (2005)]. There is also some suggestion that effects may persist into early adulthood; for example, Dietrich et al. (2001) found associations between elevated prenatal and childhood BPb concentrations and increased rates of delinquency during adolescence.

We designed the present study to expand our previous work with the Prenatal Determinants of Schizophrenia (PDS) study. As in our previous work, we capitalized on a large birth cohort in which pregnant women were recruited between 1959 and 1966. In this report, we used the New England sites of the National Collaborative Perinatal Project (NE-NCPP) (McGrath et al. 2003), whose data and design are similar to those of the PDS study. Many of the now adult offspring have been followed for neuropsychiatric outcomes. …

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