Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Apr;37(4):381-395.
doi: 10.1177/02698811231158903. Epub 2023 Mar 16.

An α7 nAChR approach for the baseline-dependent modulation of deviance detection in schizophrenia: A pilot study assessing the combined effect of CDP-choline and galantamine

Joëlle Choueiry  1   2 , Crystal M Blais  3 , Dhrasti Shah  4 , Dylan Smith  2 , Derek Fisher  5 , Alain Labelle  6 , Verner Knott  1   2   3   4   6
Affiliations
Randomized Controlled Trial

An α7 nAChR approach for the baseline-dependent modulation of deviance detection in schizophrenia: A pilot study assessing the combined effect of CDP-choline and galantamine

Joëlle Choueiry et al. J Psychopharmacol. 2023 Apr.

Abstract

Background: Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP).

Aim: The objective of this pilot study was to assess the acute effect of this combined α7 nAChR-targeted treatment (CDP-choline/galantamine) on speech MMN in patients with SCZ (N = 24) stratified by baseline MMN responses into low, medium, and high baseline auditory deviance detection subgroups.

Methods: Patients with a stable diagnosis of SCZ attended two randomized, double-blind, placebo-controlled and counter-balanced testing sessions where they received a placebo or a CDP-choline (500 mg) and galantamine (16 mg) treatment. MMN ERPs were recorded during the presentation of a fast multi-feature speech MMN paradigm including five speech deviants. Clinical measures were acquired before and after treatment administration.

Results: While no main treatment effect was observed, CDP-choline/galantamine significantly increased MMN amplitudes to frequency, duration, and vowel speech deviants in low group individuals. Individuals with higher positive and negative symptom scale negative, general, and total scores expressed the greatest MMN amplitude improvement following CDP-choline/galantamine.

Conclusions: These baseline-dependent nicotinic effects on early auditory information processing warrant different dosage and repeated administration assessments in patients with low baseline deviance detection levels.

Keywords: CDP-choline; MMN; galantamine; sensory memory; α7 nAChR.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Frontal (Fz) ERP grand averaged difference waveforms (deviant minus standard) for the five deviants during placebo and CDP-choline/galantamine (CDP-cho/gal) conditions.
Figure 2.
Figure 2.
Baseline (placebo) grand averaged frontal (Fz) difference waveforms (deviant minus standard) for the five deviants in the total sample and in LG (low), MG (medium), and HG (high) amplitude MMN subgroups. *p ⩽ 0.01.
Figure 3.
Figure 3.
Frontal (Fz) grand averaged difference waveforms (deviant minus standard) for the five deviants in LG (low), MG (medium), and HG (high) participants during placebo and CDP-choline/galantamine (CDP-cho/gal) conditions. *p < 0.05.
Figure 4.
Figure 4.
Scattergrams of treatment effect (T × Δ) amplitudes (treatment—placebo) for consonant at Fz (a, b), and vowel at Fz (c, d) correlation with PANSS total, negative, and general scores.
See this image and copyright information in PMC

References

    1. Adibhatla RM, Hatcher JF, Dempsey RJ. (2001) Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke 32: 2376–2381. - PubMed
    1. Adler LE, Cawthra EM, Donovan KA, et al.. (2005) Improved P50 auditory gating with ondansetron in medicated schizophrenia patients. Am J Psychiatry 162: 386–388. - PubMed
    1. Adler LE, Olincy A, Cawthra EM, et al.. (2004) Varied effects of atypical neuroleptics on P50 auditory gating in schizophrenia patients. Am J Psychiatry 161: 1822–1828. - PubMed
    1. Ahmed AO, Strauss GP, Buchanan RW, et al.. (2018) Schizophrenia heterogeneity revisited: Clinical, cognitive, and psychosocial correlates of statistically-derived negative symptoms subgroups. J Psychiatr Res 97: 8–15. - PubMed
    1. Aidelbaum R, Labelle A, Choueiry J, et al.. (2021) The acute dose and baseline amplitude-dependent effects of CDP-choline on deviance detection (MMN) in chronic schizophrenia: A pilot study. Exp Clin Psychopharmacol 30: 235–248. - PubMed

Publication types

MeSH terms