Pesticides and Parkinson's Disease
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports that she has participated in consulting for Biovail and clinical research trials sponsored by Boehringer-Ingleheim.
Synopsis: Elevated levels of a specific organochlorine pesticide are associated with Parkinson's disease.
Source: Richardson J R, Shalat SL, Buckley B, et al. Elevated serum pesticide levels and risk of Parkinson Disease. Arch Neurol 2009;66: 870-875.
Epidemiological studies have implicated pesticides as a possible environmental cause for Parkinson's disease (PD), but little is known about the specific toxins that may be to blame. Organochlorine pesticides are potential candidates, because they are lipophilic, highly persistent in the environment, and neurotoxic to dopaminergic neurons in rodent models. High levels of specific organochlorine pesticides have also been identified in the postmortem brains of PD patients.
In this study, the authors used a case-control study design to test the hypothesis that high serum levels of specific organochlorine pesticide(s) are associated with PD. They examined blood samples from subjects with PD (n=50) at a tertiary movement disorders center, and compared them with those of subjects with Alzheimer's disease (AD) (n=20), and healthy controls (n=43). They then used gas chromatography-mass spectrometry to test the samples for the presence of 16 different organochlorine pesticides, restricting further analysis to pesticides that were detected in at least half of the subjects with PD.
The pesticide that was most commonly detected in the serum of PD patients was ß-hexachlorocyclohexane (ß-HCH), which was present in 38/50 (76%) of PD patients, compared with 17/43 (40%) of healthy controls and 6/20 (30%) AD patients. The median level of ß-HCH was also significantly higher in subjects with PD (0.36 ng/mL) than in either control subjects (0 ng/mL) or subjects with AD (0 ng/mL). The findings raise the possibility that ß-HCH may play a role in the pathogenesis of PD.
Commentary
In spite of the rapidly growing literature about the genetic basis for PD, there remains a paucity of information about potential environmental PD risk factors. Such environmental factors may be sufficient to cause disease, or may account for the known differences in phenotype (or penetrance) between carriers of the same gene mutation.
In this study, the authors demonstrate that the presence of ß-HCH is associated with a clinical diagnosis of PD, suggesting that this organochlorine pesticide may cause or increase vulnerability to PD. Study strengths include the use of two different comparison groups - both healthy controls and subjects with AD - to exclude a non-specific association of this pesticide with neurodegenerative disorders. Limitations include the small sample size and homogeneous study sample, such that the findings may not be generalizable to other populations. Subjects in the AD group were also significantly older than the PD subjects, and thus may not have been an appropriate comparison group.
Based on the authors' findings, larger, prospective studies are warranted to clarify the potential role of ß-HCH in conferring risk for PD. Identification of environmental risk factors for PD is critical from a public health perspective, and may also provide new insights into the pathogenesis of the disease.
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