BackgroundAttention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children.ObjectiveOur goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables.MethodsWe conducted a pair-matching case–control study with 630 ADHD cases and 630 non-ADHD controls 4–12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD.ResultsThere was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs ≥ 10 μg/dL vs. ≤ 5 μg/dL; OR = 6.0; 95% confidence interval (CI) = 4.10–8.77, p < 0.01; 5–10 μg/dL vs.≤ 5 μg/dL, OR = 4.9; 95% CI = 3.47–6.98, p < 0.01]. These results were not modified by age and sex variables.ConclusionsThis was the largest sample size case–control study to date to study the association between BLLs and ADHD in Chinese children. ADHD may be an additional deleterious outcome of lead exposure during childhood, even when BLLs are < 10 μg/dL.

Lead is putatively regarded as an environmental neurotoxicant. Long-term low-level lead exposure causes cognitive deficits, but the mechanism remains to be elucidated. In the present study, the excitatory effects of low-level lead exposure on action potential (AP) firing of pyramidal neurons in CA1 region of rat hippocampal slices and the pathway through which lead induced these effects were studied with conventional whole-cell recording. Low-level lead (0.5 and 5 microM) exposure did not significantly change either voltage threshold or amplitude, duration, rise time, or rising velocity of single AP; conversely, 5 microM lead exposure significantly increased AP firing rates and reduced spike frequency adaptation. These excitatory effects of 5 microM lead were blocked by mibefradil, a selective blocker of T-type voltage-dependent calcium channels (VDCC), but not by verapamil and omega-conotoxin, selective blockers of L-type and N-type VDCC, respectively. Five micromolar lead could not change the excitability of pyramidal neurons when slices were perfused with calcium-free ACSF. In addition, the effects were abolished by inhibitors of two intracellular calcium release channels: 2-APB, an inhibitor of inositol trisphosphate receptors, and dantrolene, an inhibitor of ryanodine receptors, but not by thapsigargin, an inhibitor of endoplasmic reticulum calcium uptake. These results provide evidence for excitatory neurotoxicity of low-level lead exposure, contribution of T-type VDCC in the entrance of lead into neurons, and a possible involvement of calcium flux alteration during APs in this excitatory neurotoxicity.

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