Knott Verner, Smith Dylan, de la Salle Sara, Impey Danielle, Choueiry Joelle, Beaudry Elise, Smith Meaghan, Saghir Salman, Ilivitsky Vadim, Labelle Alain
Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada School of Psychology, University of Ottawa, Ottawa, ON, Canada Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
J Psychopharmacol. 2014 Dec;28(12):1095-108. doi: 10.1177/0269881114553254. Epub 2014 Oct 14.
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.
精神分裂症患者听觉感觉门控功能减退及相关神经认知缺陷与α7烟碱型乙酰胆碱受体（α7 nAChR）的表达和功能改变有关，针对该受体的治疗可能具有潜力。胆碱是一种选择性α7 nAChR激动剂，本研究旨在确定胞苷5'-二磷酸胆碱（CDP-胆碱），即胆碱的一种膳食来源，是否能提高根据门控水平分层的健康志愿者的感觉门控和认知能力。在一项涉及急性给予低、中剂量（500毫克、1000毫克）CDP-胆碱的随机、安慰剂对照、双盲设计中，24名健康志愿者接受了听觉门控评估，评估指标为配对刺激（S1、S2）范式中P50事件相关电位（ERP）的抑制情况，同时还通过CogState精神分裂症成套测试中的格罗顿迷宫学习任务（GMLT）测量执行功能。CDP-胆碱改善了门控（1000毫克）以及S2 P50反应的抑制（500毫克、1000毫克），其作用对门控（抑制）水平较低的个体具有选择性。对于低抑制者中GMLT表现的提高（500毫克）也有初步支持。在健康的、类似精神分裂症的替代样本中关于CDP-胆碱的这些初步发现与α7 nAChR机制一致，并支持将胆碱作为一种促认知策略进行进一步试验。
