Nicotinic enhancement of cognitive remediation training in schizophrenia

烟碱增强精神分裂症认知矫正训练

• 批准号: 8699480
• 负责人: Britta Hahn
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699480
• 关键词: Activities of Daily Living; Acute; Address; Attention; Auditory; Brain; Chronic; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Computer software; Consensus; Delusions; Educational Intervention; Employment; Enrollment; Episodic memory; Exercise; Foundations; Future; Goals; Hallucinations; Intervention; Lead; Learning; Length; Life; Marketing; Measurement; Measures; Mediating; Memory; Neurobehavioral Manifestations; Neurocognitive; Neurons; Nicotine; Nicotinic Agonists; Occupational; Outcome; Outcome Measure; Participant; Patients; Performance; Pharmaceutical Preparations; Placebos; Problem Solving; Process; Property; Quality of life; Randomized; Regimen; Research; Research Design; Resources; Schizophrenia; Science; Sensory; Sensory Process; Severities; Short-Term Memory; Smoker; Smoking Status; Structure; Subgroup; Symptoms; Testing; Time; Training; Training Programs; Visual; Withdrawal; Work; age group; alertness; base; clinically significant; cognitive function; cognitive training; computerized; effective intervention; effective therapy; executive function; functional outcomes; improved; improved functioning; information processing; neurocognitive test; non-drug; non-smoker; novel strategies; patient population; primary outcome; psychosocial; public health relevance; social cognition; success; vigilance

DESCRIPTION (provided by applicant): Cognitive deficits in schizophrenia are critically important predictors of long-term psychosocial and occupational outcome and are not significantly ameliorated by currently available medications. Cognitive remediation training can alleviate cognitive deficits associated with schizophrenia, but the impact and practicality of this approach has been limited, largely, by effect sizes and/or the time requirements needed to achieve clinically significant improvement. The proposed project is testing a novel strategy aiming at pharmacological enhancement of cognitive remediation training. Thus, rather than seeking agents capable of improving cognitive functions per se, this project is seeking to redirect efforts toward agents capable of enhancing the beneficial effects of training challenges. The prototypical nicotinic agonist nicotine facilitates sensory processing, alertness, attention, and learning and memory and thus displays an ideal effects profile for promoting training benefits. Thus, intermittent nicotine exposure during cognitive training sessions is expected to accelerate and enhance the training effects, thereby providing the proof of principle to guide the search for other, more selective compounds. Fifty people with schizophrenia will be enrolled into a 10-week, 5 days/week, computerized auditory and visual cognitive training regimen and randomized into one of two treatment groups. Every Monday and Thursday, participants in the nicotine group will receive a nicotine polacrilex lozenge (2 or 4 mg, depending on smoking status) prior to the training and participants in the placebo group a placebo lozenge. Outcome measures are neurocognitive functions assessed by the MATRICS consensus cognitive battery, level of everyday-life functioning, quality of life, and psychiatric symptoms. These measures are taken on a no-lozenge day (Wednesday) in week 0 (baseline), 4, 7, 10 and 16 (4 weeks after the intervention ends). Nicotine is expected to potentiate training-induced enhancements in these measures and to shorten the training duration necessary to induce clinically significant improvement. These results would provide proof of concept for an intervention that can markedly improve some of the most debilitating symptoms of schizophrenia. The results would also form the basis for studies of the critical training components and neuronal changes modulated by nicotine; of success rates in different patient subgroups, with different medication backgrounds, smoking status and other variables; and of more selective nicotinic agonists specifically targeted at potentiating cognitive training outcome.

描述（由申请人提供）：精神分裂症的认知缺陷是长期心理社会和职业结果的极其重要的预测因素，并且目前可用的药物无法显着改善。认知矫正训练可以缓解与精神分裂症相关的认知缺陷，但其影响和实用性 该方法在很大程度上受到效果大小和/或实现临床显着改善所需的时间要求的限制。拟议的项目正在测试一种旨在通过药理增强认知矫正训练的新策略。因此，该项目不是寻求能够改善认知功能本身的代理，而是寻求将努力转向能够增强训练挑战的有益效果的代理。典型的烟碱激动剂尼古丁促进感觉处理、警觉性、注意力以及学习和记忆，从而显示出促进训练益处的理想效果。因此，认知训练期间间歇性接触尼古丁有望加速和增强训练效果，从而提供原理证明来指导寻找其他更具选择性的化合物。 50 名精神分裂症患者将接受为期 10 周、每周 5 天的计算机化听觉和视觉认知训练方案，并随机分为两个治疗组之一。每个星期一和星期四，尼古丁组的参与者将在训练前服用尼古丁 polacrilex 含片（2 或 4 毫克，取决于吸烟状况），安慰剂组的参与者将服用安慰剂含片。结果指标是通过 MATRICS 共识认知电池评估的神经认知功能、日常生活功能水平、生活质量和精神症状。这些措施是在第 0 周（基线）、第 4、7、10 和 16 周（干预结束后 4 周）的非含片日（星期三）采取的。尼古丁有望增强训练引起的这些措施的增强，并缩短引起临床显着改善所需的训练持续时间。这些结果将为干预措施提供概念证明，该干预措施可以显着改善精神分裂症的一些最令人衰弱的症状。研究结果还将构成研究尼古丁调节的关键训练成分和神经元变化的基础；具有不同药物背景、吸烟状况和其他变量的不同患者亚组的成功率；以及专门针对增强认知训练效果的更具选择性的烟碱激动剂。