6.66 RELATIONSHIP BETWEEN ENVIRONMENTAL LEAD EXPOSURE AND NEUROCOGNITIVE PERFORMANCE IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER WITH EVIDENCE OF NORADRENERGIC GENE-LEAD INTERACTION

Objectives: We aimed to evaluate specific neurocognitive functions that are associated with blood lead levels and investigate associations of those functions with interactions between lead and dopaminergic and noradrenergic genotypes in youth with ADHD. Methods: Two hundred sixty-seven youth with ADHD and 101 healthy controls (aged 5 to 18 years) participated in this study. A semi-structured interview (K-SADS-PL) was conducted with each participant of both groups for psychiatric diagnostic evaluation. Blood lead levels were measured, and their interaction with dopaminergic or noradrenergic genotypes for ADHD, namely dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and alpha-2A-adrenergic receptor (ADRA2A) genotypes were investigated. All participants were assessed using the ADHD Rating Scale-IV (ADHD-RS), and they also completed the continuous performance test (CPT) and the Stroop color-word test (SCWT). ANCOVA was used for comparison of the blood lead levels between ADHD and control groups. Multivariable linear regression model was used to evaluate associations of blood lead levels with the results of ADHD-RS, CPT, and SCWT; IQ, age, and gender were adjusted. Path analysis model was used to identify mediating effects of neurocognitive functions between blood lead levels and ADHD symptoms. Results: There was a significant difference in blood lead levels between the ADHD and control groups (1.4±0.5 vs. 1.3±0.5 mg/dL, p=0.004). Blood lead levels showed a positive correlation with scores on omission errors of CPT (r=0.16, p=0.01) and on hyperactivity-impulsivity subscale of ADHD-RS (r=0.14, p=0.03). In the multivariable linear regression model, blood lead levels were associated with CPT omission errors (B=0.14, p=0.02). Regarding effects of lead on ADHD symptoms, hyperactivity-impulsivity were mediated by omission errors of CPT. An interaction effect was detected between ADRA2A genotype and lead level on omission errors (B=0.12, p=0.04). Conclusions: Our results showed that blood lead levels are associated with ADHD symptoms, with a mediating effect of neurocognitive functions and the neurocognitive functions are affected by the interaction between blood lead levels and noradrenergic genotype.