Small amounts of lead in the blood may increase ADHD symptoms in children who carry a specific gene variant, according to research published in Psychological Science.
Lead researcher Joel Nigg, professor of psychiatry and behavioral neuroscience at the OHSU School of Medicine, emphasizes the importance of connecting genetic susceptibility and environmental exposure. “This work helps explain one plausible pathway to ADHD and highlights how understanding gene–environment interactions could ultimately inform prevention and treatment,” he says.
In the study, researchers measured blood lead levels in 386 children ages 6 to 17. About half of these children had clinically confirmed attention-deficit/hyperactivity disorder (ADHD), while the rest served as controls. All participants had blood lead concentrations within the range the Centers for Disease Control and Prevention currently consider safe, and overall levels reflected typical values for U.S. children.
Analysis showed that the relationship between lead exposure and ADHD symptoms — especially hyperactivity and impulsivity — was stronger among children who carry the HFE C282Y gene mutation. This variant of the hemochromatosis (HFE) gene, which affects iron metabolism and can influence how the body handles lead, occurs in roughly 10 percent of U.S. children.
“Because the C282Y variant influences iron uptake and thereby modifies lead metabolism, and because the mutation was distributed randomly across the sample, our findings are difficult to explain unless lead exposure contributes causally to ADHD symptoms rather than merely being associated with them,” Nigg explains.
The effects of lead were more pronounced in boys, consistent with previous work showing sex differences in susceptibility to neurodevelopmental risks. Children without the HFE C282Y mutation also tended to show increased ADHD symptoms with higher lead levels, but that pattern was less consistent than in mutation carriers.
The investigators are careful to note that lead is not presented as the sole cause of ADHD, nor does low-level exposure guarantee an ADHD diagnosis. Instead, the study demonstrates that environmental neurotoxins such as lead can interact with genetic factors to influence behavioral outcomes and contribute to the broader explanation of ADHD.
Although public health measures in the United States have substantially lowered population-level lead exposure over recent decades, the neurotoxin remains present in everyday items and environments. Small amounts of lead can still be ingested from faded paint in older housing, contaminated dust and soil, aging water pipes, and some consumer products such as older toys or inexpensive costume jewelry. These ongoing sources make monitoring and prevention efforts important for children’s brain health.
According to the research team, these findings move the field closer to clarifying how ADHD develops in some children and may point toward targeted prevention strategies in the future: reducing environmental lead exposure and identifying genetic vulnerabilities could together lower risk.
Co-authors of the study include Alexis L. Elmore (University of Iowa), Neil Natarajan (Oregon Health & Science University), and Karen H. Friderici and Molly A. Nikolas (Michigan State University).
Funding: The research was supported by National Institute of Mental Health grants R01-MH070004, R01-MH099064, and R37-MH59015.
Source: Anna Mikulak – APS
Image Source: Image credited to Joe Mabel; licensed CC BY-SA 3.0
Original Research: Joel T. Nigg, Alexis L. Elmore, Neil Natarajan, Karen H. Friderici, and Molly A. Nikolas. DOI: 10.1177/0956797615618365
Abstract
Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children
ADHD is a heritable neurodevelopmental disorder, but environmental factors also play an important role in its development. Exposure to neurotoxins, notably lead, has been linked to adverse neurodevelopmental outcomes, including symptoms of ADHD. To assess whether the association between lead exposure and ADHD symptoms is consistent with a causal influence, the researchers employed a Mendelian randomization approach using a functional variant of the HFE gene. In a case–control design, they tested whether HFE genotype altered the strength of the association between blood lead levels and ADHD symptoms in children. The HFE gene regulates iron uptake and, by extension, affects lead metabolism. Statistical moderation by HFE genotype was observed: the association between blood lead and ADHD symptom severity varied according to functional HFE alleles, a pattern that supports a causal interpretation of lead’s contribution to ADHD-related behaviors.
Study citation: Joel T. Nigg et al., “Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children.” Published online December 28, 2015. DOI: 10.1177/0956797615618365