Systematic Evaluation of the Effects of Cognitive Remediation across Affective and Non-Affective Psychosis

认知矫正对情感性和非情感性精神病效果的系统评估

• 批准号: 9977312
• 负责人: KATHRYN Eve LEWANDOWSKI
• 金额: $ 16.4万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977312
• 关键词: Affective; Aftercare; Age; Behavior; Behavior Therapy; Bipolar Disorder; Characteristics; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Communities; Computers; Conduct Clinical Trials; Data Analyses; Data Set; Development; Diagnosis; Dimensions; Dose; Electroencephalography; Evaluation; Foundations; Funding; Goals; Hour; Intervention; Investigation; Knowledge; Literature; Measurable; Measures; Mediating; Mental disorders; Modeling; National Institute of Mental Health; Nature; Neurobehavioral Manifestations; Neuronal Plasticity; Outcome; Outcome Measure; Patients; Phenotype; Positioning Attribute; Prediction of Response to Therapy; Predictive Factor; Principal Component Analysis; Protocols documentation; Psychotic Disorders; Quality of life; Randomized Controlled Trials; Recommendation; Research; Sampling; Schizophrenia; Severities; Symptoms; System; Training; Training Programs; active control; base; brain behavior; cognitive ability; cognitive change; cognitive control; cognitive function; cognitive training; cost; disability; efficacy trial; experience; functional outcomes; implementation science; improved; information processing; neurobiological mechanism; neurophysiology; next generation; predicting response; primary outcome; profiles in patients; programs; relating to nervous system; response; secondary analysis; secondary outcome; sensory gating; treatment comparison; treatment effect; treatment response

PROJECT SUMMARY Psychotic disorders including schizophrenia [SZ] and bipolar disorder [BD] are among the most costly and debilitating psychiatric diseases worldwide. Both SZ and BD are associated with marked cognitive deficits, which are among the strongest predictors of poor community functioning, disability, and reduced quality of life (1-3). Cognitive remediation (CR) is one of the few available interventions to target cognitive symptoms directly. Growing evidence indicates that CR improves cognition in patients with these illnesses at the group level (e.g. 4-6). However, a number of critical knowledge gaps limit our ability to develop robust, individualized CR interventions and provide access to patients who are most likely to benefit: first, CR outcomes are highly heterogeneous and predictors of treatment response have not been identified; and second, the underlying neurobiological mechanisms that mediate cognitive and functional enhancement remain largely undetermined. CR trials are challenging, as interventions are often lengthy and intensive, and ascertainment and retention of patients with psychotic disorders is difficult. As a result, the majority of CR studies are underpowered to clearly identify predictors of response, compare treatment effects by diagnosis, examine the ability of CR to drive rapid neural change, and determine the extent to which neural change is associated with cognitive or functional outcomes. These knowledge gaps have limited our ability to develop robust, targeted CR programs and deliver them to patients most likely to benefit. The aims of this project are twofold: 1) identification of patient characteristics associated with cognitive treatment response including baseline demographic, clinical, and cognitive variables, and multivariate models; and 2) examination of CR's ability to drive rapid, EEG-measured neural change in key information processing systems, and the associations of this change with primary cognitive outcomes. Over the last eight years our group has completed two separate randomized controlled trials of a 70-hour CR program in patients with SZ and BD with funding from NIMH and the Brain and Behavior Research Foundation. These studies employed identical CR paradigms, active control conditions, primary (cognitive) and secondary (clinical, functional) outcome measures taken at the same timepoints (baseline, midpoint, and post-treatment), and EEG protocols. We will systematically examine moderator of CR response across the sample including demographic, clinical and cognitive variables; we will then use principal components analysis (PCA) with regression to evaluate factors predictive of CR response, compare univariate predictors with our multivariate models, and explore clustering behavior in responders vs. non-responders. Finally, we will examine early effects of CR training on EEG-measured neurophysiology, and the relationship of neural modulation to cognitive response. This project is uniquely positioned to fill critical gaps in the knowledge by merging two related datasets to form a well- powered study able to answer these questions across affective and non-affective psychosis.

项目摘要 精神病患者包括精神分裂症[SZ]和躁郁症[BD]是最昂贵的，并且 全球衰弱的精神病。 SZ和BD都与明显的认知缺陷有关， 这是社区功能不良，残疾和生活质量降低的最强预测指标之一 （1-3）。认知补救（CR）是针对认知症状的少数可用干预措施之一 直接地。越来越多的证据表明，CR可以改善该组患有这些疾病的患者的认知 级别（例如4-6）。但是，许多关键知识差距限制了我们发展强大，个性化的能力 CR干预措施并提供最有可能受益的患者的访问：首先，CR结果高度很高 尚未确定治疗反应的异质和预测指标；其次，基础 介导认知和功能增强的神经生物学机制在很大程度上仍未确定。 CR试验具有挑战性，因为干预通常是漫长而密集的，并且确定和保留 精神病患者很困难。结果，大多数CR研究都没有能力清楚 确定反应的预测指标，比较通过诊断的治疗效果，检查CR快速驱动的能力 神经变化，并确定神经变化与认知或功能相关的程度 结果。这些知识差距限制了我们制定健壮，有针对性的CR计划并提供的能力 他们给最有可能受益的患者。 该项目的目的是双重的：1）识别与认知相关的患者特征 治疗反应，包括基线人口统计学，临床和认知变量以及多元模型； 2）检查CR在关键信息处理中驱动快速，脑电图测量神经变化的能力 系统，以及这种变化与主要认知结果的关联。在过去的八年中 Group已在SZ患者中完成了70小时CR计划的两个单独的随机对照试验 和BD，并获得了NIMH以及大脑与行为研究基金会的资金。这些研究采用了 相同的CR范式，主动控制条件，主要（认知）和次级（临床，功能） 在相同时间点（基线，中点和处理后）和脑电图方案处采取的结果度量。 我们将系统地检查整个样本中CR反应的主持人，包括人口统计学，临床 和认知变量；然后，我们将使用主要组件分析（PCA）和回归来评估 预测CR响应的因素，将单变量预测因子与我们的多元模型进行比较，并探索 响应者与非反应者的聚类行为。最后，我们将检查CR培训对 脑电图测量神经生理学以及神经调节与认知反应的关系。这个项目 通过合并两个相关数据集以形成一个良好 有能力的研究能够在情感和非影响精神病中回答这些问题。