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Cited by 458Heavy Metal Exposure and ToxicityNeural and Behavioral Psychology StudiesHeavy metals in environment

Decreased Brain Volume in Adults with Childhood Lead Exposure

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Cecil, Kim M, Brubaker, Christopher J, Adler, Caleb M, Dietrich, Kim N, Altaye, Mekibib, Egelhoff, John C, Wessel, Stephanie, Elangovan, Ilayaraja +3 more·2008·PLoS Medicine
DOI 10.1371/journal.pmed.0050112PMC PMC2689675
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Abstract

BACKGROUND: Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments. METHODS AND FINDINGS: Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. CONCLUSIONS: Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.

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  • In humans, lead poisoning is associated with reductions in PFC grey matter and with various behavioural changes that arise from PFC dysfunction, including ADHD-like attentional and impulse-control problems, and even sociopathic, irresponsible and criminal behaviours.

    “In humans, lead poisoning is associated with reductions in PFC grey matter153 and with various behavioural changes that arise from PFC dysfunction, including ADHD-like attentional and impulse-control problems, and even sociopathic, irresponsible and criminal behaviours154,155.”

    From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [153]

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Authors
Cecil, K. M., Brubaker, C. J., Adler, C. M., Dietrich, K. N., Altaye, M., Egelhoff, J. C., Wessel, S., Elangovan, I., Hornung, R., Jarvis, K., & Lanphear, B. P.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Cincinnati (US)
Corresponding author
Cecil, Kim M
ORCID
Venue
PLoS Medicine
Publisher
Public Library of Science (PLoS)
Published
2008-05-27
Volume
5
Issue
5
Pages
e112
ISSN
  • 1549-1277 (ISSN-L)
  • 1549-1676
DOI
10.1371/journal.pmed.0050112
PMC
PMC2689675
OpenAlex
W2154395565
Cited by
458
References
1
Citations by year
2026: 13 · 2025: 16 · 2024: 24 · 2023: 27 · 2022: 42 · 2021: 25 · 2020: 38 · 2019: 31 · 2018: 40 · 2017: 23 · 2016: 30 · 2015: 30 · 2014: 21 · 2013: 23 · 2012: 17
FWCI
13.36
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (/ NCI R01)
  • National Cancer Institute (R01CA112182)
  • National Institute of Environmental Health Sciences (R21ES013524, ES011261, P01ES011261, ES013524, R01ES015559, ES015559)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Physical Sciences › Environmental Science › Pollution › Heavy metals in environment
Keywords
childhood lead exposure, blood lead levels, gray matter volume, brain atrophy, anterior cingulate cortex, prefrontal cortex, sex differences, fine motor function, cerebellum, brain development, executive function, neuropsychological assessment
MeSH terms
Adult, Atrophy, Brain, Brain Damage, Chronic, Cognition Disorders, Female, Humans, Lead, Lead Poisoning, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Sex Factors, Cohort Studies

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