Link Between ADHD and Lead Exposure in Kids With Genetic Mutation

Exposure to small amounts of lead may contribute to ADHD symptoms in children who have a particular gene mutation, according to new research published in Psychological Science.

“This research is valuable to the scientific community as it bridges genetic and environmental factors and helps to illustrate one possible route to ADHD. Further, it demonstrates the potential to ultimately prevent conditions like ADHD by understanding how genes and environmental exposures combine,” says lead researcher Joel Nigg, professor of psychiatry and behavioral neuroscience at the OHSU School of Medicine.

To conduct this research, Nigg and colleagues evaluated lead blood level in 386 healthy children aged 6 to 17. Half of the children had been carefully diagnosed with ADHD. All children were within the safe lead exposure range as defined by the Centers for Disease Control and Prevention, and the blood lead level in the sample was typical of the national U.S. population of children.

The analysis showed a heightened association between lead exposure and ADHD symptoms — particularly hyperactivity-impulsivity — in those with the HFE C282Y gene mutation, present in approximately 10 percent of US children.

“Because the C282Y gene helps to control the effects of lead in the body and the mutation was spread randomly in the children, the findings of our study are difficult to explain unless lead is, in fact, part of the cause of ADHD, not just an association,” explained Nigg.

The study also found that lead effects were more robust in males, which is consistent with previous research specific to neurodevelopmental conditions and gender. Children without HFE C282Y mutations showed amplified symptoms as lead exposure increased, but not as consistently.

The scientists do not purport that lead is the only cause of ADHD symptoms, nor does the research indicate that lead exposure will guarantee an ADHD diagnosis; rather, the study demonstrates that environmental pollutants, such as lead, do play a role in the explanation of ADHD.

Despite U.S. government regulations that drastically reduced environmental exposure to lead, the neurotoxin is still found in common objects such as children’s toys and costume jewelry, and continues to be ingested in small amounts via water from aging pipes, as well as contaminated soil and dust.

Image shows a sign warning of lead contamination.
The study also found that lead effects were more robust in males, which is consistent with previous research specific to neurodevelopmental conditions and gender. Children without HFE C282Y mutations showed amplified symptoms as lead exposure increased, but not as consistently. Image is for illustrative purposes only. Credit: Joe Mabel.

“Our findings put scientists one step closer to understanding this complex disorder so that we may provide better clinical diagnoses and treatment options and, eventually, learn to prevent it,” says Nigg.

About this psychology research

Co-authors on the research include Alexis L. Elmore of the University of Iowa, Neil Natarajan of Oregon Health & Science University, and Karen H. Friderici and Molly A. Nikolas of Michigan State University.

Funding: This work was supported by National Institute of Mental Health Grants R01-MH070004, R01-MH099064, and R37-MH59015.

Source: Anna Mikulak – APS
Image Source: The image is credited to Joe Mabel and is licensed CC BY-SA 3.0
Original Research: Abstract for “Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children” by Joel T. Nigg, Alexis L. Elmore, Neil Natarajan, Karen H. Friderici, and Molly A. Nikolas in Harvard Review of Psychiatr. Published online December 28 2015 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

Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis.

“Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children” by Joel T. Nigg, Alexis L. Elmore, Neil Natarajan, Karen H. Friderici, and Molly A. Nikolas in Harvard Review of Psychiatr. Published online December 28 2015 doi:10.1177/0956797615618365

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