CDP-choline: Effects of the procholine supplement on sensory gating and executive function in healthy volunteers stratified for low, medium and high P50 suppression

Abstract

Diminished auditory sensory gating and associated neurocognitive deficits in schizophrenia have been linked to altered expression and function of the alpha-7 nicotinic acetycholinergic receptor (α7 nAChR), the targeting of which may have treatment potential. Choline is a selective α7 nAChR agonist and the aim of this study was to determine whether cytidine 5'-diphosphocholine (CDP-choline), or citicoline, a dietary source of choline, increases sensory gating and cognition in healthy volunteers stratified for gating level. In a randomized, placebo-controlled, double-blind design involving acute administration of low, moderate doses (500 mg, 1000 mg) of CDP-choline, 24 healthy volunteers were assessed for auditory gating as indexed by suppression of the P50 event-related potential (ERP) in a paired-stimulus (S1, S2) paradigm, and for executive function as measured by the Groton Maze Learning Task (GMLT) of the CogState Schizophrenia Battery. CDP-choline improved gating (1000 mg) and suppression of the S2 P50 response (500 mg, 1000 mg), with the effects being selective for individuals with low gating (suppression) levels. Tentative support was also shown for increased GMLT performance (500 mg) in low suppressors. These preliminary findings with CDP-choline in a healthy, schizophrenia-like surrogate sample are consistent with a α7 nAChR mechanism and support further trials with choline as a pro-cognitive strategy.

Assessing the Acute Effects of CDP-Choline on Sensory Gating and Cognitive Deficits in Chronic Schizophrenia

“…These results are inline with previous studies analyzing the effects of selective α7 nAChR agonists and the broad spectrum agonist nicotine (Adler et al, 2005;Knott et al, 2013;Knott, Fisher, & Millar, 2010b;Koike et al, 2005;Olincy & Stevens, 2007). Furthermore, these results parallel previous acute CDP-Choline dose studies using a sample of healthy volunteers (Knott et al, 2014). Each of these studies has supported an inverted U pattern of cognitive changes in response to nAChR stimulation (i.e., optimal effects are observed with low doses).…”

“…In the same sample discussed above, sensory gating indexed by the P50 ERP was measured in response to both doses of CDP-Choline (Knott et al, 2014). The findings support a varied effect for CDP-Choline based on baseline gating ability.…”

“…Individuals participating in this study were stratified to either a low or high baseline gating ability subgroup based on their placebo P50 ratio scores. Curiously, low suppressors exhibited a reduced P50 ratio (i.e., improved gating) in response to the 1000 mg dose of CDP-Choline and to a lesser extent with the 500 mg dose (Knott et al, 2014). CDP-Choline's effects on sensory gating were specifically mediated by the suppression of the P50 response to S2 with both the 1000 mg dose and the 500 mg dose.…”

“…Its low toxicity profile, safety for long-term use, and demonstrated benefit to cognitive performance support the possibility that it may be a suitable add-on treatment aimed at the alleviation of SZ associated sensory gating deficits. Though the early evidence bolsters this likelihood (Frazier et al, 1998;Knott et al, 2014;Miller & Freedman, 1995), further research is necessary given the variability in benefit demonstrated associated with the baseline gating performance of the individual. It is possible that, as observed in healthy volunteers, the benefits associated with CDP-Choline in relation to sensory gating will only be observed in individuals demonstrating the most extreme S2 P50 amplitude suppression deficit.…”

Fetal programming of schizophrenia: Select mechanisms

“…In comparison with placebo-treated infants, choline-treated infants demonstrated better sensory gating as examined by P50 response (Ross et al, 2010). Choline supplementation was shown to enhance sensory gating measures in healthy adults as well (Knott et al, 2014). Availability of safe interventions like choline supplementation is worth exploring with large scale studies to ascertain potential preventive interventions.…”