CDP-choline and galantamine, a personalized α7 nicotinic acetylcholine receptor targeted treatment for the modulation of speech MMN indexed deviance detection in healthy volunteers: a pilot study.
Psychopharmacology (Berl). 2020 Dec;237(12):3665-3687
Authors: Choueiry J, Blais CM, Shah D, Smith D, Fisher D, Illivitsky V, Knott V
Abstract
RATIONALE: The combination of CDP-choline, an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, with galantamine, a positive allosteric modulator of nAChRs, is believed to counter the fast desensitization rate of the α7 nAChRs and may be of interest for schizophrenia (SCZ) patients. Beyond the positive and negative clinical symptoms, deficits in early auditory prediction-error processes are also observed in SCZ. Regularity violations activate these mechanisms that are indexed by electroencephalography-derived mismatch negativity (MMN) event-related potentials (ERPs) in response to auditory deviance.
OBJECTIVES/METHODS: This pilot study in thirty-three healthy humans assessed the effects of an optimized α7 nAChR strategy combining CDP-choline (500 mg) with galantamine (16 mg) on speech-elicited MMN amplitude and latency measures. The randomized, double-blinded, placebo-controlled, and counterbalanced design with a baseline stratification method allowed for assessment of individual response differences.
RESULTS: Increases in MMN generation mediated by the acute CDP-choline/galantamine treatment in individuals with low baseline MMN amplitude for frequency, intensity, duration, and vowel deviants were revealed.
CONCLUSIONS: These results, observed primarily at temporal recording sites overlying the auditory cortex, implicate α7 nAChRs in the enhancement of speech deviance detection and warrant further examination with respect to dysfunctional auditory deviance processing in individuals with SCZ.
PMID: 32851421 [PubMed - indexed for MEDLINE]
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