ADHD study supports lower lead exposure limits

A new study on potential interactions between genetic and environmental factors in ADHD suggests that current limits on lead exposure are too high. Lead exposure below the current limits allowed by Environmental Protection Agency regulations produced measurable impairment of executive functions, especially in boys, who have a specific variation in the DRD4 dopamine receptor gene.

"Even modest levels of lead exposure can cause problems," said lead author Tanya Froehlich, MD, Cincinnati Children's Hospital Medical Center. "We need to press for even lower exposure limits and we need to get the word out to families."

Dr. Froehlich looked at the interplay between lead exposure, gender, and the DRD4 gene. Lead is significantly implicated in attention and behavioral problems associated with executive functions, including planning, memory span, and attentional flexibility. A specific variation in DRD4, DRD4-7, is strongly implicated in similar executive function deficits in ADHD. Boys are more likely to have ADHD problems than girls, suggesting a gender link.

Researchers assessed the DRD4 genotype in 172 children in a community-based lead exposure study. Serum lead levels were taken at 60 months and children were given an ADHD-related administrative functions test at 66 months.

Analysis of test results identified significant associations between DRD4-7 and poorer spatial working memory, Dr. Froehlich said. Researchers also found associations between increasing serum lead levels and impaired attentional flexibility, spatial memory span, and planning. The adverse effects of lead were seen in boys, she added, but not in girls.

The most heavily impaired group in terms of attentional flexibility were boys who lacked DRD4-7. Girls and boys who had the DRD4-7 polymorphism showed no significant negative effect from lead exposure. All of the lead exposures were below current EPA limits, Dr. Froehlich noted.

"Increasing lead exposure impaired performance in boys more than girls," she said. "The result suggests that for these executive functions, boys are more vulnerable than girls and some boys are more vulnerable than others based on genetic factors. We need to set exposure standards that adequately protect the most vulnerable members of our society."