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American Journal of Epidemiology Advance Access published online on September 6, 2007
American Journal of Epidemiology, doi:10.1093/aje/kwm220
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Lead Burden and Psychiatric Symptoms and the Modifying Influence of the {delta}-Aminolevulinic Acid Dehydratase (ALAD) Polymorphism

The VA Normative Aging Study

Pradeep Rajan1,2, Karl T. Kelsey1,3,4, Joel D. Schwartz1,5, David C. Bellinger1,6, Jennifer Weuve1, David Sparrow7,8,9, Avron Spiro, III7,10, Thomas J. Smith1, Huiling Nie1,5, Howard Hu1,5,11 and Robert O. Wright1,5,12

1 Department of Environmental Health, Harvard School of Public Health, Boston, MA
2 Bureau of Environmental Disease Prevention, Division of Environmental Health, New York City Department of Health and Mental Hygiene, New York, NY
3 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA
4 Center for Environmental Health and Technology, Brown University, Providence, RI
5 The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
6 Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA
7 Veterans Affairs Boston Healthcare System, Boston, MA
8 Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA
9 Department of Medicine, Boston University School of Medicine, Boston, MA
10 Department of Epidemiology, Boston University School of Public Health, Boston, MA
11 Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI
12 Division of Emergency Medicine, Children's Hospital, Harvard Medical School, Boston, MA

Correspondence to Dr. Pradeep Rajan, Bureau of Environmental Disease Prevention, Division of Environmental Health, New York City Department of Health and Mental Hygiene, 253 Broadway, 12th Floor, CN #58, New York, NY 10007 (e-mail: prajan{at}health.nyc.gov).

Received for publication January 5, 2007. Accepted for publication June 29, 2007.

The authors evaluated the association between lead burden and psychiatric symptoms and its potential modification by a {delta}-aminolevulinic acid dehydratase (ALAD) polymorphism. Lead measurements in blood or bone and self-reported ratings on the Brief Symptom Inventory from 1991 to 2002 were available for 1,075 US men participating in the Department of Veterans Affairs (VA) Normative Aging Study. The authors estimated the prevalence odds ratio for the association between interquartile-range lead and abnormal symptom score, adjusting for potential confounders. An interquartile increment in tibia lead (14 µg/g) was associated with 21% higher odds of somatization (95% confidence interval of the odds ratio: 1.01, 1.46). An interquartile increment in patella lead (20 µg/g) corresponded to a 23% increase in the odds of global distress (95% confidence interval of the odds ratio: 1.02, 1.47). An interquartile increment in blood lead (2.8 µg/dl) was associated with 14% higher odds of hostility (95% confidence interval of the odds ratio: 1.02, 1.27). In all other analyses, lead was nonsignificantly associated with psychiatric symptoms. The adverse association of lead with abnormal mood scores was generally stronger among ALAD 1-1 carriers than 1-2/2-2 carriers, particularly regarding phobic anxiety symptoms (pinteraction = 0.004). These results augment evidence of a deleterious association between lead and psychiatric symptoms.

blood; bone and bones; lead; neuropsychological tests; polymorphism; genetic

Abbreviations: ALAD, {delta}-aminolevulinic acid dehydratase; CI, confidence interval


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