Joelle Choueiry1,2,3, Crystal M Blais4, Dhrasti Shah5, Dylan Smith6,7,5, Derek Fisher8, Vadim Illivitsky6, Verner Knott9,6,7,4,5. 1. Department of Neuroscience, Faculty of Medicine, University of Ottawa, 1145 Carling Ave, Ottawa, ON, K1Z 7K4, Canada. joelle.choueiry@theroyal.ca. 2. Department of Psychiatry, The Royal Ottawa Mental Health Centre, Ottawa, ON, Canada. joelle.choueiry@theroyal.ca. 3. Department of Psychology, University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. joelle.choueiry@theroyal.ca. 4. Institute of Cognitive Science, Carleton University, Ottawa, ON, Canada. 5. School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, ON, Canada. 6. Department of Psychiatry, The Royal Ottawa Mental Health Centre, Ottawa, ON, Canada. 7. Department of Psychology, University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. 8. Department of Psychology, Faculty of Social Sciences, Mount Saint Vincent University, Halifax, NS, Canada. 9. Department of Neuroscience, Faculty of Medicine, University of Ottawa, 1145 Carling Ave, Ottawa, ON, K1Z 7K4, Canada.
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.
RCT Entities:
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.
Authors: Lawrence E Adler; Ellen M Cawthra; Kara A Donovan; Josette G Harris; Herbert T Nagamoto; Ann Olincy; Merilyne C Waldo Journal: Am J Psychiatry Date: 2005-02 Impact factor: 18.112
Authors: Lawrence E Adler; Ann Olincy; Ellen M Cawthra; Kara A McRae; Josette G Harris; Herbert T Nagamoto; Merilyne C Waldo; Mei-Hua Hall; Amanda Bowles; Laurie Woodward; Randal G Ross; Robert Freedman Journal: Am J Psychiatry Date: 2004-10 Impact factor: 18.112