Clinical Neuroscience of Schizophrenia Laboratory.
Schizophrenia Program.
Exp Clin Psychopharmacol. 2022 Apr;30(2):235-248. doi: 10.1037/pha0000418. Epub 2021 Feb 25.
The detection of deviant auditory features is empirically supported as impaired in schizophrenia and has been shown to associate with functional outcome. Modulated by glutamate neurotransmission, this sensory process has also been shown to relate to the α7 nicotinic acetylcholine receptor (nAChR) system, a prioritized molecular target for the development of novel cognition targeted pharmacological treatments. This pilot study assessed the acute effects of CDP-Choline, a choline supplement with α7 nAChR agonist properties, on the mismatch negativity (MMN), an event-related potential index of the detection of an acoustic change, in a sample of individuals diagnosed with chronic schizophrenia. Utilizing a randomized, placebo-controlled, double-blind design, the dose-dependent (500 mg, 1,000 mg, 2,000 mg), baseline amplitude-dependent (low vs. high), and deviant feature-dependent effects of CDP-Choline on the MMN were examined. CDP-choline's effects interacted with dosage, deviance feature, and baseline amplitude with low baseline amplitude patients demonstrating enhanced MMNs, and high baseline amplitude patients demonstrating suppressed MMNs in response to CDP-Choline. These findings offer tentative support for the involvement of the α7 nAChR system in auditory MMN abnormalities in schizophrenia and supports further research assessing the effects of long-term treatment with CDP-Choline in the personalized treatment of auditory deviance processing impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
听觉特征异常的检测在精神分裂症中被经验证存在障碍,并与功能结果相关。受谷氨酸能神经传递调制,该感觉过程也与α7 烟碱型乙酰胆碱受体 (nAChR) 系统相关,该系统是开发新型靶向认知药理学治疗的优先分子靶标。这项初步研究评估了 CDP-胆碱(一种具有 α7 nAChR 激动剂特性的胆碱补充剂)对匹配负变(MMN)的急性影响,MMN 是对声音变化检测的事件相关电位指数,该研究在一组被诊断为慢性精神分裂症的个体中进行。利用随机、安慰剂对照、双盲设计,研究了 CDP-胆碱的剂量依赖性(500mg、1000mg、2000mg)、基线幅度依赖性(低 vs. 高)和偏差特征依赖性对 MMN 的影响。CDP-胆碱的作用与剂量、偏差特征和基线幅度相互作用,低基线幅度患者的 MMN 增强,高基线幅度患者的 MMN 抑制。这些发现为 α7 nAChR 系统参与精神分裂症听觉 MMN 异常提供了初步支持,并支持进一步研究评估长期使用 CDP-胆碱治疗对听觉偏差处理障碍的个性化治疗的效果。