Get the Lead Out!
Abstract & Commentary
By Allan J. Wilke, MD, MA, Professor and Chair, Department of Integrative Medicine, Ross University (Bahamas) Limited, Freeport, Grand Bahama, The Bahamas. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Low-level lead intoxication, known to adversely affect young children's cognitive development and behavior, may also harm young adults.
Source: Bouchard MF, et al. Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in U.S. young adults. Arch Gen Psychiatry 2009; 66:1313-1319.
Using data from the national health and nutrition Examination Survey (NHANES), these researchers investigated the association between blood lead levels (BLLs) and psychiatric illnesses in young adults with a cross-sectional epidemiological survey. The dataset included 1987 individuals who had been administered the World Health Organization Composite International Diagnostic Interview (CIDI) to identify major depressive disorder (MDD), panic disorder (PD), and generalized anxiety disorder (GAD). The individuals ranged in age from 20 to 39 years and 55% were female. NHANES is designed to be a national sample and the race/ethnicity composition of this sample reflects that of the country. MDD was diagnosed in 134 respondents (7%), PD in 44 (2%), and GAD in 47 (2%). Some respondents had more than one diagnosis. The mean BLL was 1.61 µg/dL and ranged from 0.3 to 37.3 µg/dL. Levels were higher in men, older individuals, Mexican Americans, less well-educated, and smokers. When the blood levels were divided into quintiles, after appropriate adjustment, odds ratios (OR) for MDD and PD, but not for GAD, were greater with increasing BLL concentrations. The OR for MDD, comparing the lowest quintile with the highest quintile, was 2.32 (confidence interval [CI], 1.13-4.75) and for PD was 4.94 (CI, 1.32-18.48). Since smoking cigarettes is associated with higher blood lead levels and with psychiatric disorders, the investigators repeated the analysis after excluding smokers. The results were essentially unchanged: MDD 2.92 (CI, 1.24-6.92) and PD 9.57 (CI, 1.28-71.43).
Commentary
Since a randomized controlled study exposing individuals to lead is highly unlikely, this study may be the best we can do until larger studies replicate it. I mention size, because it is one of the weaknesses of this study. In the analysis of PD, for example, after excluding smokers, only 14 of 1359 persons were so afflicted, and this is reflected in the wide confidence interval. As with all studies of this sort, causation is not established. On the other hand, accepting reverse causation means explaining why young adults with MDD or PD go out of their way to intoxicate themselves with lead. One plausible explanation goes like this: Persons with psychiatric conditions tend to smoke cigarettes more than folks without those problems. Tobacco can be contaminated with lead. Hence, significantly depressed or panicky persons are accidentally intoxicating themselves. Refuting this argument is the finding that the results hold even when smokers are excluded.
I think it helps to put this article into the context of lead poisoning, also known as plumbism. Reviewing quickly, lead poisoning has been recognized since at least the second century BCE.1 Acute poisoning results in abdominal pain and a host of other gastrointestinal side effects, paresthesias, hemoglobinuria, and muscle weakness. Chronic poisoning can include other neurological symptoms, such as memory loss and depression. Adults historically have developed lead poisoning from occupational exposure, although there are other sources, such as spiking wine with lead acetate to sweeten it. Children, by contrast, are usually the victims of environmental pollution. Physicians of my generation will remember the initial efforts to rid our country of sources of lead, including the removal of tetraethyl lead as a gasoline additive and banning lead-based house paints. This has not eliminated the danger worldwide, as developing countries still use leaded gasoline and children are still sickened by lead in ceramic glazes and lead-containing "traditional" medicines,2 by living near lead smelters, or by exposure to lead dust introduced by parents who work at smelters or lead-acid battery plants.3 As late as 2007, toys imported from China were found to have unacceptably high concentrations of lead in their paint.4
Ingested lead appears in blood, tissue, and bone, where its half-life is measured in years. BLLs do not correlate to total body lead burden. In children, BLLs < 10 µg/dL are associated with decreased cognitive function, developmental delays, and behavior problems,5 and Medicaid mandates screening of children with 10 µg/dL as the cutoff.6 Although we have made progress in reducing elevated BLLs in children, in 2004, 1.4% of screened children still had BLLs > 10 µg/dL.7 Consider now that the mean BLL in these young adults was 1.61 µg/dL and, in the highest quintile, the low end of BLLs was only 2.11 µg/dL. In the NHANES 1999-2002, the mean BLL in adults was 1.64 µg/dL.8 In a recently published study, kidney function was reduced in adolescents with BLLs < 10 µg/dL.9
If lead at these levels can affect children and adolescents, is it too great a leap to assume that very low BLLs can cause MDD and PD in adults? Now what? Do you screen all your depressed patients for elevated BLLs? If you find an elevated BLL, do you recommend chelation, even though there is no evidence for efficacy of lead chelation, except in moderate and severe intoxication?10 I believe that, for now, learning what, if any, exposure all of your patients have to lead is best, along with reducing individual exposure and advocating for reduction of lead environmental pollution. There may be no "safe" level of lead exposure.
References
1. Pearce JM. Burton's line in lead poisoning. Eur Neurol 2007;57:118-119.
2. Karri SK, et al. Lead encephalopathy due to traditional medicines. Curr Drug Saf 2008;3:54-59.
3. Centers for Disease Control and Prevention. Childhood lead poisoning associated with lead dust contamination of family vehicles and child safety seats Maine, 2008. MMWR Morb Mortal Wkly Rep 2009;58:890-893.
4. Mattel CEO: 'Rigorous standards' after massive toy recall. Available at: www.cnn.com/2007/US/08/14/recall/index.html. Accessed Jan. 3, 2010.
5. Canfield RL, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003;348:1517-1526.
6. Centers for Disease Control and Prevention. Screening young children for lead poisoning: Guidance for state and local public health officials. Atlanta, GA: U.S. Department of Health and Human Services; 1997. Available at www.cdc.gov/nceh/lead/guide/guide97.htm. Accessed Jan. 3, 2010.
7. Jones RL, et al. Trends in blood lead levels and blood lead testing among US children aged 1 to 5 years, 1988-2004. Pediatrics 2009;123:e376-e385.
8. Muntner P, et al. Continued decline in blood lead levels among adults in the United States: The National Health and Nutrition Examination Surveys. Arch Intern Med 2005; 165:2155-2161.
9. Fadrowski JJ, et al. Blood lead level and kidney function in U.S. adolescents. Arch Intern Med 2010;170:75-82.
10. Bradberry S, Vale A. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Clin Toxicol (Phila) 2009;47:841-858.
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