One of the most consistent risk factors for Parkinson's disease (PD) is lack of cigarette smoking (odds ratio ~ 2.5). This association extends to smoking habits decades prior to diagnosis. One possibility is that in PD patients, early mild loss of dopamine may influence substance use or other behaviors decades before development of motor abnormalities. We hypothesize that in a large group of PD patients, smoking history may be significantly associated both with the dopamine-related personality trait "novelty seeking" and with [18F]fluorodopa uptake in anteroventral striatum. Dopaminergic influences on novelty seeking, smoking initiation, and smoking cessation may each map to different mesencephalic projection areas, such as caudate, nucleus accumbens, or prefrontal cortex.
In a large group of PD patients and normal controls, we will map regions of the brain in which dopamine innervation corresponds to smoking history or to novelty seeking. We will then test whether nonsmoking or low novelty seeking is associated with lower [18F]fluorodopa uptake in at-risk relatives in the brain regions previously identified. This research may help resolve the direction of causation of the PD-nonsmoking association and shed light on the biology of addiction and personality. The results may also suggest improved measures for prediction of PD in at-risk individuals or improved measures of response to putative neuroprotective therapies.
We will ascertain smoking history and a measure of novelty seeking (the TCI-R-140 Likert version of Cloninger's TCI) in a large sample of PD patients and healthy controls who have already had [18F]fluorodopa positron emission tomography (FD PET) scans. Additionally, we propose new pilot imaging studies in first-degree relatives of PD patients with the same smoking and personality assessments.