Low Blood Lead Levels Associated with Clinically Diagnosed Attention-Deficit/Hyperactivity Disorder and Mediated by Weak Cognitive Control

Joel T. Nigg, G. Mark Knottnerus, Michelle M. Martel, Molly Nikolas, Kevin Cavanagh, Wilfried Karmaus, Marsha D. Rappley

Research output: Contribution to journalArticlepeer-review

206 Scopus citations


Background: Attention-deficit/hyperactivity disorder (ADHD) and low-level lead exposure are high-prevalence conditions among children, and studies of large populations have suggested that these conditions are related. We examine this relationship in children from a community sample exposed to average background levels of lead who have a diagnosis of ADHD that is established by clinical criteria. Methods: One hundred fifty children ages 8-17 years participated (mean age = 14 years; 53 control subjects, 47 ADHD Predominantly Inattentive type, 50 ADHD-Combined type). Diagnosis was formally established with a semi-structured clinical interview and parent and teacher ratings. Children completed intelligence quotient (IQ) measures and the stop task (a neuropsychological measure). Lead was assayed from whole blood with inductively coupled plasma mass spectrometry. Results: Blood lead levels in this sample closely matched US population exposure averages, with a maximum level of 3.4 μg/dL. Blood lead levels were statistically significantly higher in ADHD-combined type than in non-ADHD control (p < .05) children. Blood lead was associated with symptoms of hyperactivity-impulsivity but not inattention-disorganization, after control of covariates. Blood lead levels were linked with a lower IQ (p < .05), but IQ did not account for effects on hyperactivity. Instead, hyperactivity mediated effects of lead on IQ. Effects of blood lead on hyperactivity-impulsivity were mediated by poor performance on the stop task. This mediation effect was independent of effects of lead on IQ. Conclusions: Low-level lead exposure might be an important contributor to ADHD. Its effects seem to be mediated by less effective cognitive control, consistent with a route of influence via striatal-frontal neural circuits.

Original languageEnglish
Pages (from-to)325-331
Number of pages7
JournalBiological Psychiatry
Issue number3
StatePublished - Feb 1 2008

Bibliographical note

Funding Information:
This work was supported by R21 MH 070542 (PI: JTN) and by an MSU HBRI grant for data collection and laboratory analyses and by funding from CDC via Public Health Preparedness and Response for Bioterrorism to Michigan Department of Community Health that partially supported the laboratory analysis.


  • ADHD
  • blood lead
  • cognitive control
  • hyperactivity

ASJC Scopus subject areas

  • Biological Psychiatry


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