Background: Lead exposure, a dopamine receptor D4 polymorphism (DRD4-7), and sex have been linked to ADHD or ADHD-related neuropsychological deficits. Interactions between these three factors are biologically plausible, but have not been previously examined.
Methods: DRD4 genotype and 60 month blood lead level were assessed in 172 children. At 66 months, children were administered measures affiliated with spatial working memory, rule learning and reversal, spatial span, and planning. Multivariable analyses were used to examine main effects and interactions of lead, DRD4, and sex on these executive functions.
Results: DRD4-7 was associated with poorer spatial working memory, and incryeasing blood lead levels were associated with impaired rule learning and reversal, spatial span, and planning. Lead’s adverse effects on planning and rule learning and reversal were seen primarily for boys. In addition, lead’s impact on rule learning and reversal was evident predominately for those lacking DRD4-7.
Conclusions: We observed independent effects of DRD4-7 and lead on various executive functions, and modifications of lead s effects by DRD4 genotype and sex. This study offers a model for examining how genes, toxicants, and sex interact to shape the endophenotypes underlying ADHD.