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社会心理和职业成果的重要预测指标，当前可用的药物没有显着改善。认知补救培训可以减轻与精神分裂症相关的认知缺陷，但这种影响和实用性 在很大程度上，通过有效的大小和/或实现临床显着改善所需的时间要求有限。拟议的项目正在测试一种旨在增强认知补救培训的药理策略的新型策略。因此，该项目不是寻求能够改善认知功能的代理人，而是寻求将努力重定向到能够增强培训挑战的有益作用的代理。典型的烟碱激动剂尼古丁促进了感觉处理，警觉性，注意力以及学习和记忆，因此显示出促进培训益处的理想效果。因此，预计在认知训练期间间歇性尼古丁暴露将加速并增强训练效果，从而提供原理证明，以指导搜索其他更具选择性的化合物。 50人患有精神分裂症的人将入学为期10周，5天/周，计算机化的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，尼古丁小组的参与者将在培训之前获得尼古丁polacrilex lozenge（2或4毫克，具体取决于吸烟状态），并在安慰剂组A安慰剂lozenge中获得。结果指标是通过基督教认知电池，日常生活功能，生活质量和精神病症状评估的神经认知功能。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）中采取的。尼古丁有望在这些措施中增强训练引起的增强，并缩短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最令人衰弱的症状。结果还将构成研究关键训练成分和尼古丁调节神经元变化的基础。不同患者亚组的成功率，具有不同的药物背景，吸烟状况和其他变量；以及专门针对增强认知训练结果的更具选择性的烟碱激动剂。