Biological Psychiatry
Volume 63, Issue 3 , Pages 325-331, 1 February 2008

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

  • Joel T. Nigg

      Affiliations

    • Department of Psychology, Michigan State University, East Lansing
    • Corresponding Author InformationAddress reprint requests to Joel T. Nigg, Ph.D., 115 Psychology Building, Michigan State University, East Lansing MI 48824-1116
    • ,
  • G. Mark Knottnerus

      Affiliations

    • State of Michigan Department of Community Health, Bureau of Labs, Lansing, Michigan
    • ,
  • Michelle M. Martel

      Affiliations

    • Department of Psychology, Michigan State University, East Lansing
    • ,
  • Molly Nikolas

      Affiliations

    • Department of Psychology, Michigan State University, East Lansing
    • ,
  • Kevin Cavanagh

      Affiliations

    • State of Michigan Department of Community Health, Bureau of Labs, Lansing, Michigan
    • ,
  • Wilfried Karmaus

      Affiliations

    • University of South Carolina, Department of Epidemiology and Biostatistics, Columbia, South Carolina.
    • ,
  • Marsha D. Rappley

      Affiliations

    • Department of Pediatrics, Michigan State University, East Lansing

Received 30 March 2007; received in revised form 1 July 2007; accepted 3 July 2007. published online 17 September 2007.

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.

Key Words: ADHD, blood lead, cognitive control, hyperactivity

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 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.

 All authors report no biomedical financial interests or potential conflicts of interest.

PII: S0006-3223(07)00675-0

doi:10.1016/j.biopsych.2007.07.013

Biological Psychiatry
Volume 63, Issue 3 , Pages 325-331, 1 February 2008

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