Combining CDP-choline and galantamine, an optimized α7 nicotinic strategy, to ameliorate sensory gating to speech stimuli in schizophrenia

Abstract

Neural α7 nicotinic acetylcholine receptor (nAChR) expression and functioning deficits have been extensively associated with cognitive and early sensory gating (SG) impairments in schizophrenia (SCZ) patients and their relatives. SG, the suppression of irrelevant and redundant stimuli, is measured in a conditioning-testing (S1-S2) paradigm eliciting electroencephalography-derived P50 event-related potentials (ERPs), the S2 amplitudes of which are typically suppressed relative to S1. Despite extensive reports of nicotine-related improvements and several decades of research, an efficient nicotinic treatment has yet to be approved for SCZ. Following reports of SG improvements in low P50 suppressing SCZ patients and healthy participants with the α7 agonist, CDP-choline, this pilot study examined the combined modulatory effect of CDP-choline (500 mg) and galantamine (16 mg), a nAChR positive allosteric modulator and acetylcholinesterase inhibitor, on SG to speech stimuli in twenty-four SCZ patients in a randomized, double-blind and placebo-controlled design. As expected, in low P50 suppressors CDP-choline/galantamine (vs. Placebo) improved rP50 and dP50 scores by increasing inhibitory mechanisms as reflected by S2P50 amplitude reductions. Results also suggest a moderating role for auditory verbal hallucinations in treatment response. These preliminary findings provide supportive evidence for the involvement of α7 nAChR activity in speech gating in SCZ and support additional trials, examining different dose combinations and repeated doses of this optimized and personalized targeted α7 cholinergic treatment for SG dysfunction in subgroups of SCZ patients.