Efficacy of Personalizing Cognitive Remediation for Schizophrenia by Targeting Impairments in Early Auditory Processing

针对早期听觉处理损伤的个性化认知疗法对精神分裂症的疗效

• 批准号: 10240285
• 负责人: Alice Medalia
• 金额: $ 51.01万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240285
• 关键词: Activities of Daily Living; Address; Adult; Aftercare; Area; Auditory; Client; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Consensus; Custom; Data; Diagnosis; Electroencephalography; Enrollment; Exercise; Goals; Grant; Impaired cognition; Impairment; Individual; Infrastructure; Intervention; Judgment; Knowledge; Learning; Literature; Measures; Mediating; Mediation; Mental Health Services; Mental disorders; Outcome; Outpatients; Participant; Perception; Performance; Population; Public Health; Randomized; Recovery; Research; Sample Size; Schizoaffective Disorders; Schizophrenia; Services; Specificity; Subgroup; System; Technology; Testing; Therapeutic; Training; Verbal Learning; auditory processing; base; clinical decision-making; cognitive benefits; cognitive enhancement; cognitive function; cognitive skill; cognitive training; community clinic; computerized; confirmatory clinical trial; daily functioning; design; disability; evidence base; experience; functional gain; functional outcomes; improved; individualized medicine; metropolitan; neurobehavioral; neurophysiology; patient subsets; personalized medicine; primary outcome; programs; prospective; randomized controlled design; relating to nervous system; response; schizophrenia-spectrum disorder; secondary outcome; skills; therapeutic target; treatment as usual; treatment optimization; treatment planning; treatment response; treatment strategy

Schizophrenia is associated with cognitive deficits that negatively impact daily functioning. Interventions that improve cognitive functioning in schizophrenia are critical to limit long-term disability. Cognitive remediation (CR) for schizophrenia has low moderate effect sizes on cognitive and functional outcomes, but therapeutic responses to CR are heterogeneous. Prospective identification of treatment-responsive individuals and individualized treatment approaches remains an unmet challenge. Our preliminary studies using personalized CR approaches for schizophrenia indicate that baseline early auditory processing (EAP), which is impaired in about half of people with schizophrenia, is a good neurobehavioral marker for informing treatment strategy. We found that people with baseline impaired EAP improve significantly more on cognitive outcomes when CR includes EAP training, and this facilitates larger functional gain. However, there is no added benefit to giving this training to people with baseline intact EAP. Subgroup specificity of therapeutic mechanism is suggested by the positive association of auditory processing gain with cognitive improvement among EAP impaired versus the negative or non-significant association among those who are EAP intact. These findings support the importance of addressing basic auditory processing deficits when attempting to remediate higher order auditory impairments such as verbal learning. In addition, they highlight the need for routine assessment of EAP in CR participants, so treatment can be personalized. Pilot data from an ongoing center grant project indicates that clinicians are able to assess EAP status and use it to personalize treatment to either include or exclude EAP training. Thus it is feasible to implement this kind of personalized CR in public clinic settings. The proposed study uses a treatment controlled randomized design, first stratifying subjects by EAP status and then randomizing to EAP enhanced CR, regular CR, or treatment as usual. The study will be conducted in community clinics using the infrastructure of the ongoing center grant CR project. Cognition will be the primary outcome with functional capacity the secondary outcome. Mobile EEG administered to CR participants will examine neurophysiologic markers of need for and response to EAP training. Mediation analysis will examine whether gains in cognition mediate the relationship between gains in EAP and functional outcome. This will inform our understanding of EAP as the therapeutic change mechanism for about half of CR participants and confirm that EAP training need not be given to those CR participants with baseline intact EAP. The goal of this study is to enhance CR outcomes in schizophrenia spectrum disorders by identifying a scalable approach to optimizing and personalizing treatment. By facilitating a better understanding of EAP as a neurobehavioral marker, early auditory processing as mechanism of change, and the essential CR treatment targets for EAP impaired CR participants, the proposed 4-year study will inform improved clinical decision- making and guide clinical judgment about how to best provide cognitive training.

精神分裂症与认知缺陷有关，对日常功能产生负面影响。干预措施 改善精神分裂症的认知功能对于限制长期残疾至关重要。认知的 精神分裂症的修复（CR）对认知和功能结果的影响较低，但 对CR的治疗反应是异质的。预期识别治疗响应的个体 个性化的治疗方法仍然是一个未满足的挑战。我们使用的初步研究 精神分裂症的个性化CR方法表明基线早期听觉处理（EAP）是 大约一半的精神分裂症患者受损，是一个很好的神经行为标记，用于治疗 战略。我们发现，基线受损的人EAP的人在认知结果上有了更大的改善 当CR包括EAP训练时，这有助于更大的功能增益。但是，没有其他好处 向基线完整EAP的人进行此培训。治疗机制的亚组特异性是 由听觉加工增益与EAP之间的认知改善的积极关联所暗示 与EAP完整的人之间的障碍与负面或不重要的关联。这些发现 支持在试图纠正更高时解决基本听觉处理缺陷的重要性 订购听觉障碍，例如言语学习。此外，他们强调了进行常规评估的需求 CR参与者的EAP，因此可以个性化治疗。正在进行的中心赠款项目的试点数据 表明临床医生能够评估EAP状态并将其用于个性化治疗以包括或 排除EAP培训。因此，在公共诊所环境中实施这种个性化的CR是可行的。 拟议的研究使用治疗控制的随机设计，首先通过EAP对受试者进行分层。 状态，然后像往常一样随机进行EAP增强CR，常规CR或治疗。该研究将是 使用正在进行的中心赠款CR项目的基础设施在社区诊所进行。认知会 成为功能能力的主要结果。移动脑电图施用到CR 参与者将检查对EAP培训的需求和反应的神经生理标记。调解 分析将检查认知的收益是否介导了EAP和功能中的增益之间的关系 结果。这将使我们对EAP的理解是大约一半CR的治疗变化机制 参与者并确认不必为基线完整EAP的CR参与者提供EAP培训。 这项研究的目的是通过识别一个 可扩展的方法来优化和个性化处理。通过促进对EAP的更好理解 Neurobehavioral标记，早期听觉处理作为变化的机制和必需的CR治疗 EAP受损的CR参与者的目标，拟议的4年研究将为改进的临床决策提供信息 - 关于如何最好地提供认知培训的临床判断。