title: Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor.
abstract: Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3+/-15.5 vs. 65.5+/-14.2 years, p=0.94). Mean log blood harmane concentration was approximately 50% higher in cases than controls (0.50+/-0.54g(-10)/ml vs. 0.35+/-0.62g(-10)/ml, p=0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR(adjusted) 1.56, 95% CI 1.01-2.42, p=0.04), and odds of ET was 1.90 (95% CI 1.07-3.39, p=0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53+/-0.57g(-10)/ml), intermediate in cases with sporadic ET (0.43+/-0.45g(-10)/ml) and lowest in controls (0.35+/-0.62g(-10)/ml) (test for trend, p=0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.
authors.affiliation: GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. EDL2@columbia.edu
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.forename: Wendy
authors.initials: W
authors.lastname: Jiang
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Pellegrino
authors.forename: Eileen
authors.initials: E
authors.lastname: Rios
authors.forename: Pam
authors.initials: P
authors.lastname: Factor-Litvak
authors.forename: Claire
authors.initials: C
authors.lastname: Henchcliffe
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004785:Environmental Pollutants / Q000009:adverse effects / Q000097:blood*; D020329:Essential Tremor / Q000097:blood* / Q000139:chemically induced / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006247:Harmine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D004785:Environmental Pollutants; D006247:Harmine; C005010:harman