PDF(Pubmed)
Abstract：
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).
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.
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.
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.
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.
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.
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.
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.
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.
摘要：
未经证实：精神分裂症（SCZ）患者的认知操作（包括注意力前感觉处理）明显受损，但有证据表明个体间存在显著异质性，其缓和与烟碱乙酰胆碱受体（nAChR）激动剂的治疗反应。先前在健康志愿者中的研究表明，单独使用α7nAChR激动剂胞苷5'-二磷酸胆碱（CDP-胆碱）以及与烟碱变构调节剂（加兰他敏）联合使用对听觉偏差检测的基线依赖性影响，该听觉偏差检测用负失配（MMN）事件相关电位（ERP）测量。
UNASSIGNED：这项初步研究的目的是评估这种联合的α7nAChR靶向治疗（CDP-胆碱/加兰他敏）对SCZ（N=24）患者语音MMN的急性影响，中等,和高基线听觉偏差检测亚组。
UNASSIGNED：SCZ诊断稳定的患者参加了两个随机分组，双盲,他们接受安慰剂或CDP-胆碱(500mg)和加兰他敏(16mg)治疗的安慰剂对照和反平衡试验。在演示包括五个语音偏差的快速多特征语音MMN范例期间记录了MMNERP。在治疗给药之前和之后获得临床测量。
未经评估：虽然没有观察到主要治疗效果，CDP-胆碱/加兰他敏显着增加MMN振幅到频率，持续时间,低群个体的元音语音偏差。阳性和阴性症状量表阴性较高的个体，一般,和总分表示在CDP-胆碱/加兰他敏之后最大的MMN振幅改善。
UNASSIGNED：这些对早期听觉信息处理的基线依赖性烟碱效应需要对基线偏差检测水平低的患者进行不同剂量和重复给药评估。
UNASSIGNED：这项初步研究的目的是评估这种联合的α7nAChR靶向治疗（CDP-胆碱/加兰他敏）对SCZ（N=24）患者语音MMN的急性影响，中等,和高基线听觉偏差检测亚组。
UNASSIGNED：SCZ诊断稳定的患者参加了两个随机分组，双盲,他们接受安慰剂或CDP-胆碱(500mg)和加兰他敏(16mg)治疗的安慰剂对照和反平衡试验。在演示包括五个语音偏差的快速多特征语音MMN范例期间记录了MMNERP。在治疗给药之前和之后获得临床测量。
未经评估：虽然没有观察到主要治疗效果，CDP-胆碱/加兰他敏显着增加MMN振幅到频率，持续时间,低群个体的元音语音偏差。阳性和阴性症状量表阴性较高的个体，一般,和总分表示在CDP-胆碱/加兰他敏之后最大的MMN振幅改善。
UNASSIGNED：这些对早期听觉信息处理的基线依赖性烟碱效应需要对基线偏差检测水平低的患者进行不同剂量和重复给药评估。
