Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

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 ∼50% higher in cases than controls (0.50 ± 0.54 g^-10/ml vs. 0.35 ± 0.62 g^-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 ± 0.57 g^-10/ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g^-10/ml) and lowest in controls (0.35 ± 0.62 g^-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.