Efficacy of a Cognitive Remediation Treatment Program for Bipolar Disorder

双相情感障碍认知矫正治疗方案的疗效

• 批准号: 8604753
• 负责人: KATHRYN Eve LEWANDOWSKI
• 金额: $ 14.99万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604753
• 关键词: Address; Adult; Age; Area; Award; Behavioral; Bipolar Disorder; Brain; Characteristics; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Collaborations; Communities; Computers; Control Groups; Development; Diagnosis; Disease; Dose; Elements; Environment; Evaluation; Exhibits; Functional disorder; Funding; Future; Goals; Health; Hospitals; Hour; Image; Impaired cognition; Intervention; Intervention Studies; Investigation; K-Series Research Career Programs; Measures; Mediating; Mediator of activation protein; Mental Health; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; National Institute of Mental Health; Neurobehavioral Manifestations; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurosciences; Onset of illness; Outcome; Outcome Study; Outpatients; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phenotype; Populations at Risk; Positioning Attribute; Protocols documentation; Psychologist; Psychopathology; Psychotic Disorders; Public Health; Randomized; Recommendation; Recording of previous events; Recruitment Activity; Research; Research Personnel; Research Project Grants; Research Support; Review Literature; Sampling; Schizoaffective Disorders; Schizophrenia; Scientist; Secondary to; Secure; Site; Symptoms; Techniques; Time; Training; Training Programs; Treatment outcome; Work; base; career; cognitive change; cognitive enhancement; cognitive function; cognitive neuroscience; design; executive function; experience; fitness; functional improvement; functional outcomes; improved; insight; instructor; interest; knowledge base; medical schools; neuroimaging; novel; patient oriented research; processing speed; programs; psychosocial; severe mental illness; skills; treatment program; visual memory

DESCRIPTION (provided by applicant): This is an application for a K23-Mentored Patient-Oriented Research Career Development Award entitled "Efficacy of a Cognitive Remediation Treatment Program for Bipolar Disorder". The candidate is an instructor and assistant research psychologist at McLean Hospital/Harvard Medical School with a background in neurocognitive and behavioral deficits in patients with psychosis and at risk populations. Clinically, the candidate has focused on treatment of adults with severe and persistent mental illness, including patients with schizophrenia (SZ), schizoaffective disorder (SZA), and bipolar disorder (BD). The candidate's work in cognitive phenotypes of psychotic illness and her clinical interests have converged on an interest in the implementation of novel treatment approaches to address cognitive dysfunction in psychosis. She now aims to apply her research and clinical experience to psychosocial clinical trials work specifically targeting neurocognitive dysfunction in patients with BD with psychosis and, ultimately, other psychotic illnesses. Cognitive dysfunction is increasingly recognized as a major feature of BD, present by illness onset, persistent into euthymia, and associated with functional outcome. Deficits are qualitatively similar to those seen in SZ, and may be quantitatively similar in some patient groups (50-55), e.g. in patients with a history of psychosis. Despite strong associations between cognitive impairment and functional outcomes in BD, treatment for these symptoms at present is inadequate. Pharmacotherapies do little to address cognitive symptoms, and may even worsen them. Psychosocial cognitive remediation (CR) treatments have been developed to target these symptoms and their functional correlates, and have shown early promise in patients with SZ in improving both neurocognition and community functioning. However, despite the overlap of neurocognitive deficits between patients with SZ and BD, no studies to date have extended neuroscience- based CR to patients with BD. The present proposal aims to assess the efficacy of CR treatment in patients with BD with a history of psychosis using a 70-hour CR paradigm compared to a dose- matched computer-based control. It is hypothesized that patients in the CR group will exhibit improvements in cognitive and community functioning compared to controls, which will persist during a 6-month durability phase. Additionally, putative mechanisms of functional change will be examined, including mediator effects of cognitive and clinical change on community functioning. 130 patients with BD with a history of psychosis recruited from the Psychotic Disorders Programs at McLean Hospital will be randomized into either the CR or computer control group. CR will be administered using the PositScience Brain Fitness and InSight programs, neuroscience-based training programs that have shown early promise in patients with SZ and are used actively by the Mentor (Dr. Keshavan) and an Advisor (Dr. Vinogradov) on this project. Participants will be assessed on measures of clinical, cognitive, and community functioning at baseline, following the 70-hour treatment or control phase, and again 6 months later. This project is in keeping with the NIH's stated strategic priorities for improving mental health outcomes in patients and strengthening the impact of NIMH-supported research on public health, with specific recommendations for broad implementation of effective psychosocial interventions. The candidate's research examining neurocognition across diagnoses and over time, and her pilot work examining CR in patients with psychosis indicate that a) patients with BD exhibit significant and persistent neurocognitive deficits, b) CR is well-tolerated in patients with BD with psychosis, c) the candidate has access to patients who are appropriate for the proposed study, and d) the candidate can develop and implement longitudinal and treatment-outcome studies of neurocognition in patients with psychotic illness. As an instructor and assistant research psychologist at McLean Hospital/Harvard Medical School, the candidate is well positioned to continue to develop her work toward a career as an independent investigator. She has gained extensive experience with patient oriented research, and now seeks additional training in clinical trials work, CR techniques, quantitative methods, and cognitive neuroscience techniques (including neuroimaging) in order to develop expertise in CR clinical trials and a knowledge base in cognitive neuroscience. Training in these areas is necessary for the development of her academic identity as a clinical scientist conducting independent investigations of CR in BD and other major psychotic illnesses. Additionally, in future work the candidate aims to develop collaborations with experts in cognitive neuroscience and imaging toward identifying mechanisms of cognitive change after CR treatment. The candidate has assembled a team of mentors and advisors for this project who are experts in CR (including the use of the CR programs selected for the present proposal), clinical trails, outcomes in bipolar disorder, quantitative methods in longitudinal research, and cognitive neuroscience and neuroimaging, and with whom she has demonstrated effective and productive collaborations. Additionally, a number of courses have been selected in key training areas, and are available to her through Harvard and its affiliates. Together with the rich training environment of McLean Hospital - Harvard's largest psychiatric training site - the above mentorship and didactics will allow the candidate to develop the skills and expertise necessary to transition to an independent research career, and, by the end of the award period, to develop next phase research projects and secure federal funding in order to undertake them.

描述（由申请人提供）：这是一份 K23 指导的以患者为导向的研究职业发展奖的申请，题为“双相情感障碍认知矫正治疗计划的功效”。该候选人是麦克莱恩医院/哈佛医学院的讲师和助理研究心理学家，具有精神病患者和高危人群的神经认知和行为缺陷的背景。在临床上，该候选人专注于治疗患有严重和持续性精神疾病的成人，包括精神分裂症（SZ）、分裂情感性障碍（SZA）和双相情感障碍（BD）患者。该候选人在精神病认知表型方面的工作和她的临床兴趣集中在对实施新的治疗方法来解决精神病认知功能障碍的兴趣上。她现在的目标是将她的研究和临床经验应用于心理社会临床试验工作，专门针对患有精神病以及最终其他精神病的双相情感障碍患者的神经认知功能障碍。认知功能障碍越来越被认为是双相情感障碍的一个主要特征，它表现为疾病发作，持续到情绪正常，并与功能结果相关。缺陷在质量上与 SZ 中所见的缺陷相似，并且在某些患者组 (50-55) 中可能在数量上相似，例如有精神病史的患者。尽管双相情感障碍的认知障碍和功能结果之间存在密切关联，但目前对这些症状的治疗还不够。药物疗法对解决认知症状效果甚微，甚至可能使症状恶化。社会心理认知矫正 (CR) 治疗方法就是针对这些症状及其功能相关性而开发的，并且已经在精神分裂症患者中显示出在改善神经认知和社区功能方面的早期前景。然而，尽管 SZ 和 BD 患者之间的神经认知缺陷有重叠，但迄今为止还没有研究将基于神经科学的 CR 扩展到 BD 患者。本提案旨在使用 70 小时 CR 范式与剂量匹配的基于计算机的对照相比，评估 CR 治疗对有精神病史的 BD 患者的疗效。据推测，与对照组相比，CR 组患者的认知和社区功能将有所改善，并且这种改善将在 6 个月的持久阶段持续存在。此外，还将研究功能变化的假定机制，包括认知和临床变化对社区功能的中介影响。从 McLean 医院精神病项目招募的 130 名有精神病史的 BD 患者将被随机分为 CR 组或计算机对照组。 CR 将使用 PositScience Brain Fitness 和 InSight 计划进行管理，这些基于神经科学的培训计划已在 SZ 患者中显示出早期前景，并被该项目的导师（Keshavan 博士）和顾问（Vinogradov 博士）积极使用。参与者将在基线、70 小时治疗或控制阶段之后以及 6 个月后再次接受临床、认知和社区功能测量的评估。该项目符合 NIH 规定的改善患者心理健康结果和加强 NIMH 支持的研究对公共卫生影响的战略重点，并为广泛实施有效的社会心理干预措施提出了具体建议。该候选人的研究跨诊断和随时间推移检查神经认知，以及她检查精神病患者 CR 的试点工作表明：a) BD 患者表现出显着且持续的神经认知缺陷，b) CR 在患有精神病的 BD 患者中具有良好的耐受性，c) 候选人可以接触到适合拟议研究的患者，d) 候选人可以开发和实施神经认知的纵向和治疗结果研究 患有精神病的患者。作为麦克莱恩医院/哈佛医学院的讲师和助理研究心理学家，候选人有能力继续发展她的工作，成为一名独立调查员。她在以患者为导向的研究方面获得了丰富的经验，现在寻求临床试验工作、CR 技术、定量方法和认知神经科学技术（包括神经影像学）方面的额外培训，以发展 CR 临床试验的专业知识和认知神经科学的知识库。这些领域的培训对于发展她作为一名临床科学家的学术身份是必要的，她对双相情感障碍和其他主要精神疾病的 CR 进行独立调查。此外，在未来的工作中，候选人的目标是与认知神经科学和影像学专家开展合作，以确定 CR 治疗后认知变化的机制。候选人为该项目组建了一支由导师和顾问组成的团队，他们是 CR（包括为本提案选择的 CR 项目的使用）、临床试验、双相情感障碍的结果、纵向研究的定量方法以及认知神经科学和神经影像学方面的专家，并且她与他们展示了有效和富有成效的合作。此外，她还在关键培训领域选择了一些课程，并通过哈佛大学及其附属机构向她提供这些课程。加上哈佛最大的精神病学培训场所麦克莱恩医院丰富的培训环境，上述指导和教学将使候选人能够发展过渡到独立研究职业所需的技能和专业知识，并在奖励期结束时开发下一阶段的研究项目并获得联邦资助以开展这些项目。