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: 10676816
• 负责人: Alice Medalia
• 金额: $ 48.59万
• 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/10676816
• 关键词: Activities of Daily Living; Address; Adult; Aftercare; Area; Auditory; Client; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Data; Diagnosis; Electroencephalography; Enrollment; Exclusion; Exercise; Goals; Grant; Impaired cognition; Impairment; Individual; Infrastructure; Intervention; Judgment; Knowledge; Learning; Literature; MATRICS Consensus Cognitive Battery; Measures; Mediating; Mediation; Mental Health Services; Mental disorders; Outcome; Outpatients; Participant; Perception; Performance; Persons; Pilot Projects; Population; Public Health; Randomized; Recovery; Research; Sample Size; Schizoaffective Disorders; Schizophrenia; Services; Specificity; Subgroup; System; Technology; Testing; Therapeutic; Training; Verbal Learning; auditory processing; 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; neural; neurobehavioral; neurophysiology; patient subsets; personalized medicine; primary outcome; programs; prospective; randomized controlled design; remediation; 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，会对日常功能产生负面影响。干预措施 改善精神分裂症认知功能对于限制长期残疾至关重要。认知的 精神分裂症的补救（CR）对认知和功能结果的影响程度较低，但是 CR 的治疗反应是异质的。前瞻性识别治疗反应个体 个体化治疗方法仍然是一个尚未解决的挑战。我们的初步研究使用 精神分裂症的个性化 CR 方法表明基线早期听觉处理 (EAP) 大约一半的精神分裂症患者的神经行为受损，是指导治疗的良好神经行为标志物 战略。我们发现 EAP 基线受损的人的认知结果有显着改善 当 CR 包括 EAP 训练时，这有助于获得更大的功能增益。然而，没有任何额外的好处 向具有完整 EAP 基线的人员提供此培训。治疗机制的亚组特异性是 EAP 中听觉处理增益与认知改善呈正相关 受损与 EAP 完好的人之间的负相关或不显着相关。这些发现 支持在尝试纠正更高的听觉处理缺陷时解决基本听觉处理缺陷的重要性 顺序听觉障碍，例如语言学习。此外，他们还强调了进行常规评估的必要性 CR 参与者中的 EAP，因此治疗可以个性化。来自正在进行的中心拨款项目的试点数据 表明临床医生能够评估 EAP 状态并使用它来个性化治疗，包括或 排除 EAP 培训。因此，在公共诊所实施这种个性化 CR 是可行的。 拟议的研究采用治疗控制随机设计，首先根据 EAP 对受试者进行分层 状态，然后随机分为 EAP 增强 CR、常规 CR 或照常治疗。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 是主要结果，功能能力是次要结果。 CR 进行移动脑电图检查 参与者将检查 EAP 训练的需求和反应的神经生理学标志。调解 分析将检验认知增益是否调节 EAP 增益和功能增益之间的关系 结果。这将有助于我们理解 EAP 作为大约一半 CR 的治疗改变机制 参与者，并确认 EAP 培训不需要对基线完整 EAP 的 CR 参与者进行。 本研究的目的是通过确定一种方法来增强精神分裂症谱系障碍的 CR 结局 优化和个性化治疗的可扩展方法。通过促进人们更好地理解 EAP 神经行为标志物、早期听觉处理作为变化机制以及必要的 CR 治疗 EAP 受损 CR 参与者的目标，拟议的 4 年研究将为改善临床决策提供信息 - 制定并指导如何最好地提供认知训练的临床判断。

项目成果

Disparities in technology literacy and access negatively impact cognitive remediation scalability.

• DOI: 10.1016/j.schres.2022.04.006
• 发表时间: 2022-05
• 期刊: SCHIZOPHRENIA RESEARCH
• 影响因子: 4.5
• 作者: Arlia, Christina;Saperstein, Alice M.;Meyler, Shanique;Styke, Sarah;Medalia, Alice
• 通讯作者: Medalia, Alice