Sleep disturbance as a putative mechanism for reward system dysfunction

睡眠障碍是奖励系统功能障碍的假定机制

• 批准号: 8700073
• 负责人: Patrick Finan
• 金额: $ 16.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700073
• 关键词: Address; Affect; Affective; American; Area; Basic Science; Behavior Therapy; Behavioral; Behavioral Model; Behavioral Sciences; Brain; Caring; Chronic; Clinical; Clinical Research; Clinical Services; Comorbidity; Corpus striatum structure; Data; Decision Making; Development; Dopamine; Emotions; Failure; Functional disorder; Future; Goals; Health; Heroin Users; Human; Individual; Laboratories; Longitudinal Studies; Measures; Mentored Patient-Oriented Research Career Development Award; Methods; Motivation; Musculoskeletal Pain; Neurobiology; Neurotransmitters; Opiate Addiction; Opioid; Pain; Pain management; Pathway interactions; Patient Self-Report; Patients; Perception; Persons; Polysomnography; Population; Process; Protocols documentation; Psychophysiology; Public Health; Quality of Care; Readiness; Recruitment Activity; Relapse; Reporting; Research; Research Personnel; Research Project Grants; Research Training; Rewards; Risk Factors; Sampling; Self Management; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Slide; Stimulus; Symptoms; System; Testing; Training; Woman; Work; actigraphy; addiction; base; behavior measurement; biobehavior; chronic pain; coping; dependence relapse; emotion regulation; experience; forging; improved; innovation; interest; men; neural circuit; neuroimaging; novel; outcome forecast; pre-clinical; prescription opioid abuse; primary outcome; programs; psychopharmacologic; public health relevance; research study; response; responsible research conduct; skills; tool

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award (K23) proposal includes a coordinated training plan and research project that will facilitate the Candidate's transition to independent investigator. It will provide the Candidate with the tools to become a leading expert on the basic human behavioral science behind the association of sleep disturbance and reward system function, and to develop an independent program of basic and clinical research on the interrelations of sleep disturbance, the reward system, and chronic pain in opioid-dependent patients. This topic area is important because opioid dependence is a growing public health problem, sleep disturbance and chronic pain are increasingly recognized as prevalent and problematic comorbidities, and understanding how sleep disturbance alters behavioral and affective measures of reward system function may enhance the limited treatment options for opioid-dependent patients with chronic pain. Long-term, the Candidate's program of research will employ a multimodal assessment strategy involving human biobehavioral laboratory experiments and longitudinal clinical research. The Candidate will need to become well-versed in the pathophysiological and neurobiological underpinnings of sleep and the reward system. Specific short-term training goals are: 1) Gain expertise in experimental sleep methods and assessment of sleep disturbance; 2) Gain training in the neurobiology and assessment of the reward system; 3) Gain training in research with opioid-dependent patients and 4) Gain training in the responsible conduct of research. The proposed short-term development activities will enable the Candidate to achieve his long-term goals by providing the necessary skill set to a) safely and effectively manipulate sleep; b) objectively measure sleep psychophysiology; c) objectively measure behavioral reward system function d) confidently interpret evidence of functional reward system changes from a biobehavioral perspective; e) recruit, retain, and responsibly execute research protocols with opioid dependent patients; and f) understand the psychopharmacological basis of opioid addiction and the clinical nuances of comorbid chronic pain. The proposed research project is divided into 2 studies. Study 1 will establish a basic behavioral model of sleep disturbance-induced reward system dysfunction in a within-person sleep deprivation experiment with healthy subjects. Study 2 will gather cross-sectional pilot data to determine if the association of sleep disturbance with reward system dysfunction is greater in opioid-dependent patients with versus without chronic pain. The coordinated training and research plans logically extend from the Candidate's prior work on emotion regulation in chronic musculoskeletal pain, and forge a novel research direction that addresses gaps in our current understanding of how sleep disturbance affects reward system function, and how that pathway contributes to chronic pain in patients with opioid dependence.

描述（由申请人提供）：这项受过指导的面向患者的研究职业发展奖（K23）提案包括一个协调的培训计划和研究项目，将促进候选人向独立研究者的过渡。它将为候选人提供工具，以成为睡眠障碍和奖励系统功能关联背后的基本人类行为科学的领先专家，并开发有关阿片类药物依赖性患者的睡眠障碍，奖励系统以及慢性疼痛的基本和临床研究的独立计划。该主题领域很重要，因为阿片类药物的依赖性是日益增长的公共卫生问题，睡眠障碍和慢性疼痛越来越被认为是普遍和有问题的合并症，并且了解睡眠障碍如何改变行为和情感奖励系统功能的情感度量可能会增强阿片类药物依赖慢性疼痛的有限治疗方案。长期，候选人的研究计划将采用涉及人类生物行为实验室实验和纵向临床研究的多模式评估策略。候选人将需要在睡眠和奖励系统的病理生理学和神经生物学基础上进行精心设计。特定的短期培训目标是：1）在实验睡眠方法中获得专业知识和睡眠障碍评估； 2）获得奖励系统神经生物学和评估的培训； 3）接受与阿片类药物依赖性患者的研究培训，4）在负责任的研究中获得培训。拟议的短期发展活动将使候选人通过提供必要的技能来实现其长期目标，以安全有效地操纵睡眠； b）客观地衡量睡眠心理生理学； c）客观地衡量行为奖励系统d）自信地解释功能奖励系统从生物行为的角度变化的证据； e）招募，保留和负责任地与阿片类药物患者一起执行研究方案； f）了解阿片类药物成瘾的心理药理基础和合并症慢性疼痛的临床细微差别。拟议的研究项目分为两项研究。研究1将在健康受试者的人体睡眠剥夺实验中建立睡眠障碍引起的奖励系统功能障碍的基本行为模型。研究2将收集横断面试验数据，以确定阿片类药物依赖性患者与无慢性疼痛的患者的睡眠障碍与奖励系统功能障碍的关联是否更大。逻辑上从候选人的慢性肌肉骨骼疼痛中的情绪调节工作逻辑上扩展了协调的培训和研究计划，并为我们当前对睡眠障碍如何影响奖励系统功能的理解以及该途径如何对患者的慢性疼痛有何影响。