Academic journal article Environmental Health Perspectives

Prenatal Lead Exposure, [Delta]-Aminolevulinic Acid, and Schizophrenia

Academic journal article Environmental Health Perspectives

Prenatal Lead Exposure, [Delta]-Aminolevulinic Acid, and Schizophrenia

Article excerpt

Schizophrenia is a severe mental disorder of unknown etiology. Recent reports suggest that a number of environmental factors during prenatal development may be associated with schizophrenia. We tested the hypothesis that environmental lead exposure may be associated with schizophrenia using archived serum samples from a cohort of live births enrolled between 1959 and 1966 in Oakland, California. Cases of schizophrenia spectrum disorder were identified and matched to controls. A biologic marker of lead exposure, [delta]-aminolevulinic acid ([delta]-ALA), was determined in second-trimester serum samples of 44 cases and 75 controls. [delta]-ALA was stratified into high and low categories, yielding 66 subjects in the high category, corresponding to a blood lead level (BPb) [greater than or equal to] 15 [micro]g/dL, and 53 in the low category, corresponding to BPb < 15 [micro]g/dL. Using logistic regression, the odds ratio (OR) for schizophrenia associated with higher [delta]-ALA was 1.83 [95% confidence interval (CI), 0.87-3.87; p = 0.1]. Adjusting for covariates gave an OR of 2.43 (95% CI, 0.9%5.96; p = 0.051). This finding suggests that the effects of prenatal exposure to lead and/or elevated [delta]-ALA may extend into later life and must be further investigated as risk factors for adult psychiatric diseases. Key words: [delta]-aminolevulinic acid, developmental, lead, Pb, prenatal, prospective, psychosis, schizophrenia. Environ Health Perspect 112:548-552 (2004). doi:10.1289/ehp.6777 available via http://dx.doi.org/[Online 8 January 2004]

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Schizophrenia and related disorders are characterized by hallucinations, delusions, social withdrawal, and disorganized thinking. Although typically diagnosed during late adolescence and early adulthood, a growing body of evidence suggests that events during prenatal development may play a role in the etiology of these diseases. In particular, exposures to agents that may disrupt or damage the developing nervous system have been implicated. This theory, commonly referred to as the "neurodevelopmental hypothesis of schizophrenia" (Murray et al. 1992; Weinberger et al. 1996), has been supported by recent findings that suggest prenatal nutritional deprivation and infection may be risk factors for schizophrenia (Susser et al. 1999). However, few investigators have considered schizophrenia among the possible neuropsychiatric sequelae of chemical agents.

Lead, a known chemical teratogen, is capable of disrupting both behavioral and physical development (Sobotka and Rahwan 1995). Relationships between early exposure to lead and neuropsychologic abnormalities have been observed throughout the life course (Bellinger et al. 1991; Kim et al. 1995; Pocock et al. 1994). For example, the Yugoslavia Prospective Study reported that lead exposure during midpregnancy was associated with deficits in neoropsychiatric function at 24 months of age (Factor-Litvak et al. 1999; Graziano et al. 1990). Further assessments of the cohort identified persistent decrements in measures of attention, cognition, and verbal comprehension at 4, 7, 10, and 12 years of age (Wasserman et al. 2000). Needleman et al. (1979, 1990) found associations between dentine lead levels measured in deciduous teeth (6-8 years of age) and reading difficulties and failure to graduate from high school.

In a prospective study conducted in Cincinnati, Ohio, prenatal and average childhood blood lead concentrations were reported to be associated with increased delinquent behavior later in life (Dietrich et al. 2001). This suggests that prenatal lead exposure may be a risk factor for other adolescent and adult-onset outcomes, possibly psychiatric disorders. Schizophrenia is one plausible candidate because some of its premorbid features such as reduced attention, neurocognitive impairment, and diminished educational attainment (Jones et al. 1993) strongly resemble the behavioral deficits associated with lead exposure. …

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