Targeted α7 Nicotinic Acetylcholine Receptor Treatment for the Modulation of Speech MMN in Schizophrenia: An Optimized CDP-Choline and Galantamine Combination Approach Personalized to Baseline-Deviance Detection Levels

Abstract

α7 nicotinic acetylcholine receptors (nAChR) pathophysiology is associated with sensory and cognitive dysfunction in schizophrenia (SCZ), a multigenic neurodevelopmental disorder. The mismatch negativity event-related potential (MMN-ERP) is sensitive to early deviance detection and sensory memory processing, which are impaired in SCZ and their non-affected relatives. Improvement in MMN amplitudes is associated with clinical and functional outcomes, making this ERP an ideal endophenotype to assess novel pharmacological treatments. As genetics, smoking status, personality, and functioning level were emphasized as trait factors underlying response variability to pharmacological therapies and specific α7 nAChR agonists, the MMN use for participant baseline electrophysiological response stratification is an increasingly applied strategy demonstrating converging evidence of deviance detection improvements in SCZ. Evidence for sensory processing improvements mediated by α7 nAChR-agonists and considering this receptor’s fast desensitization rate, a novel optimized approach combining CDP-choline (a selective α7 agonist) with galantamine (a nAChR positive allosteric modulator) was shown to increase deviance detection in healthy low-baseline groups.