Study first to confirm causal link between lead exposure and ADHD

Genetics and environmental factors jointly contribute to the effects of attention deficit hyperactivity disorder

PORTLAND, Ore. – Scientists at OHSU Doernbecher Children's Hospital have defined the first causal link between blood lead exposure and attention deficit hyperactivity disorder in humans. While previous studies have associated lead blood levels with ADHD, research published in Psychological Science is the first to confirm previous hypotheses that exposure to lead in miniscule amounts typical in the U.S., or less than 10 parts per billion, increases symptoms in some individuals with ADHD. 

"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,” said Joel Nigg, Ph.D., principal investigator; director, OHSU ADHD & Attention Research Program; director, Division of Psychology, OHSU Doernbecher Children's Hospital; and professor of psychiatry and behavioral neuroscience, 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.

Their analysis showed a heightened causal link between lead exposure and ADHD symptoms -- particularly hyperactivity-impulsivity -- in those with the HFE C282Y gene mutation, which is present in approximately 10 percent of U.S. 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. It also continues to be ingested in small amounts via water from aging pipes, as well as contaminated soil and dust. At very high levels, lead poisoning may result in seizures, coma or even death. However, long term, lower-level exposures are a more common health threat, particularly in children. 

"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,” said Nigg.

The paper "Variation in iron metabolism gene moderates the association between low-level blood lead exposure and Attention-Deficit/Hyperactivity Disorder” is a collaboration among researchers at OHSU Doernbecher Children's Hospital, Michigan State University and the University of Iowa.

This study was supported by the National Institute of Mental Health (R37- MH059105 and R01-MH070004).

About OHSU Doernbecher Children's Hospital

OHSU Doernbecher Children's Hospital ranks among the nation's Best Children's Hospitals,* is one of 21 members of the Children's Oncology Group's Phase 1 and Pilot Consortium.  Nationally recognized physicians and nurses provide a full range of specialty and subspecialty care to tens of thousands of children annually, resulting in 200,000 discharges, surgeries, transports and outpatient visits annually in a patient- and family-centered environment. OHSU Doernbecher providers also travel throughout Oregon and Southwest Washington, providing specialty care to more than 3,000 children at more than 200 outreach clinics in 15 locations. Using state-of-the-art, secure two-way video and audio communication, OHSU Doernbecher's Telemedicine Network connects pediatric intensivists and neonatologists to emergency room physicians statewide to help evaluate time-critical pediatric patient needs and assist with treatment plans.

News source: