Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease.

BACKGROUND: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. OBJECTIVE: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. METHODS: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). RESULTS: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. CONCLUSION: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

Changes in thalamus-hypothalamus serotonin transporter availability during clomipramine administration in patients with obsessive-compulsive disorder.

To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [(123)I] beta-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I] beta-CIT brain binding was used (BP(ND)=(thalamus and hypothalamus-cerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72+/-0.12 vs 1.39+/-0.18, p<0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r=-0.46; p<0.05 and r=-0.53; p<0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B=14.145+/-4.514; t=3.133; p=0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

Sleep microstructure and neurodegeneration as measured by [123I]beta-CIT SPECT in treated patients with Parkinson's disease.

OBJECTIVES: Along with spindles, K-complexes are well known hallmarks of stage 2 (S2) sleep. However, little is known about their quantity in S2 sleep of patients with Parkinson's disease (PD). SETTING: Sleep laboratory, Department of Neurology, University of Vienna, Austria. PATIENTS AND METHODS: Whole-night polysomnography (PSG) was performed in twelve treated PD patients and ten healthy controls without history of sleep complaints. The quantity of spontaneous K-complexes, K-alpha-complexes, and sleep spindles in one hour S2 sleep, distributed in four epochs of 15 minutes all through the night, were visually selected and analysed. The quantity and the temporal course of these phasic events were compared with the quantity in age-matched healthy controls. Nine of the twelve PD patients underwent [123I]beta-CIT SPECT for calculating dopamine transporter binding in the striatum and serotonin transporter density in the thalamus-hypothalamus region. RESULTS: There was no difference between the quantity of K-complexes, K-alpha-complexes, and sleep spindles in PD patients and in the healthy control group. K-complexes but not sleep spindles decreased over the night in both groups. The number of sleep spindles did not correlate with the dopamine transporter binding in the striatum or the serotonin binding in the thalamic/hypothalamic region. CONCLUSION: K-complexes and sleep spindles are not reduced and do not seem to be related to the degree of dopaminergic degeneration in treated PD patients.

Chronic thalamic stimulation in a patient with spinocerebellar ataxia type 2.

We report on a patient with spinocerebellar ataxia type 2 (SCA 2) with an unusual clinical presentation, including severe, disabling resting and action tremor and the successful treatment of this tremor syndrome with chronic thalamic stimulation. Using [(123)I]beta-CIT single photon emission computed tomography, we document a marked degeneration of the nigrostriatal dopaminergic system in SCA 2.