Higher blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations correlate with lower olfactory scores in essential tremor.
BACKGROUND
Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease.


OBJECTIVE
To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET.


METHODS
Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT).


RESULTS
In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho=-0.46, p<0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted odd ratios (OR) 4.04, 95% confidence intervals (CI) 1.42-11.50, p=0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho=0.12, p=0.32).


CONCLUSIONS
Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET.
Louis
Elan D
ED
GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. EDL2@columbia.edu
Rios
Eileen
E
Pellegrino
Kathryn M
KM
Jiang
Wendy
W
Factor-Litvak
Pam
P
Zheng
Wei
W
D000368:Aged; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000473:pathology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D020329:Essential Tremor / Q000523:psychology*; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives* / Q000097:blood / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009498:Neurotoxins / Q000097:blood* / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects*; D012903:Smell / Q000187:drug effects*
D009498:Neurotoxins; D006247:Harmine; C005010:harman