Efficacy of a Cognitive Remediation Treatment Program for Bipolar Disorder

描述（由申请人提供）：这是一份申请k23指导的患者导向研究职业发展奖的申请，题为“双相情感障碍认知补救治疗计划的疗效”。候选人是麦克林医院/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。候选人在精神疾病的认知表型方面的工作和她的临床兴趣集中在对解决精神病认知功能障碍的新治疗方法的实施感兴趣。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，专门针对双相障碍合并精神病患者的神经认知功能障碍，并最终针对其他精神疾病。认知功能障碍越来越被认为是双相障碍的一个主要特征，从发病开始就存在，持续到精神状态，并与功能预后相关。缺陷在质量上与SZ相似，在某些患者组（50-55岁）中可能在数量上相似，例如有精神病史的患者。尽管认知障碍和双相障碍的功能结局之间有很强的联系，但目前对这些症状的治疗还不充分。药物治疗对解决认知症状几乎没有作用，甚至可能使症状恶化。社会心理认知修复（CR）治疗已经开发出针对这些症状及其功能相关的治疗方法，并在SZ患者中显示出改善神经认知和社区功能的早期希望。然而，尽管SZ和BD患者之间存在神经认知缺陷的重叠，迄今为止还没有研究将基于神经科学的CR扩展到BD患者。本研究旨在通过70小时CR范式与剂量匹配的基于计算机的对照，评估CR治疗有精神病史的BD患者的疗效。假设与对照组相比，CR组患者在认知和社区功能方面表现出改善，这种改善将持续6个月的持久期。此外，功能变化的假设机制将被检查，包括认知和临床变化对社区功能的中介作用。从麦克莱恩医院精神障碍项目招募的130名有精神病史的双相障碍患者将被随机分为CR组和计算机对照组。CR将使用PositScience脑健康和InSight项目进行管理，这是基于神经科学的培训项目，在SZ患者中显示出早期的希望，并被导师（Keshavan博士）和顾问（Vinogradov博士）积极使用。在70小时的治疗或控制阶段，以及6个月后，参与者将在基线时进行临床、认知和社区功能的评估。该项目符合美国国立卫生研究院提出的战略优先事项，即改善患者的心理健康结果，加强nimh支持的研究对公共卫生的影响，并为广泛实施有效的社会心理干预提出了具体建议。候选人在诊断和时间上检查神经认知的研究，以及她在精神病患者中检查CR的试点工作表明，a)双相障碍患者表现出显著和持续的神经认知缺陷，b) CR在患有精神病的双相障碍患者中具有良好的耐受性，c)候选人可以接触到适合该研究的患者。d)候选人可以开发和实施精神疾病患者神经认知的纵向和治疗结果研究。作为麦克林医院/哈佛医学院的讲师和助理研究心理学家，候选人很好地定位于继续发展她作为独立调查员的职业生涯。她在以患者为导向的研究方面获得了丰富的经验，现在正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她作为临床科学家在双相障碍和其他主要精神疾病中进行CR独立调查的学术身份的发展是必要的。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合作，以确定CR治疗后认知变化的机制。该候选人为该项目组建了一个导师和顾问团队，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，并且她已经证明了有效和富有成效的合作。此外，她还通过哈佛及其附属机构选择了一些关键培训领域的课程。加上哈佛大学最大的精神病学培训基地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发展到独立研究生涯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，并获得联邦资金以承担这些项目。

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.