Optimizing placebo effects in depressed older adults: Enhancing processing speed and executive functioning with computerized cognitive training

优化抑郁老年人的安慰剂效应：通过计算机认知训练提高处理速度和执行功能

• 批准号: 10194015
• 负责人: JOEL R. SNEED
• 金额: $ 40.67万
• 依托单位: QUEENS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194015
• 关键词: Address; Adult; Age; Amygdaloid structure; Antidepressive Agents; Behavior; Belief; Brain region; Cerebrovascular Disorders; Chronic; Clinical assessments; Complex; Depressed mood; Development; Disease remission; Elderly; Escitalopram; Executive Dysfunction; Exercise; Expectancy; Failure; Functional disorder; Goals; Impairment; Intervention; Investigational Therapies; Knowledge; Laboratories; Longevity; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Modeling; Morbidity - disease rate; National Institute of Mental Health; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Outcome; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Placebo Effect; Placebos; Population; Prefrontal Cortex; Prevention; Public Health; Quality of life; Randomized; Recurrence; Research; Residual state; Rest; Role; Selective Serotonin Reuptake Inhibitor; Signal Transduction; Strategic Planning; Structure; Symptoms; Technology; Testing; Training; Translations; Treatment outcome; Ventral Striatum; White Matter Hyperintensity; active control; base; cognitive control; cognitive function; cognitive process; cognitive reappraisal; cognitive training; computerized; depressive symptoms; design; digital; disability; executive function; expectation; geriatric depression; improved; indexing; mortality; neural circuit; neuromechanism; novel; novel therapeutics; pill; processing speed; recruit; response; therapy resistant; treatment response

PROJECT SUMMARY: Major Depressive Disorder (MDD) is a leading cause of disability, morbidity, and mortality across the lifespan and poses a particularly severe public health problem in late life. Late-life depression (LLD) is highly recurrent, can become chronic, and is often difficult to treat. Antidepressant treatment is often ineffective in this population because of the presence of neurocognitive factors including slow processing speed (PS), executive dysfunction (ED), and cerebrovascular disease (CVD) that interfere with treatment. It is crucial, therefore, that we develop interventions that address antidepressant non-response and dramatically improve the quality of life of millions of vulnerable older adults. We recently determined that an important cause of non- response in this population is impaired expectancy effects, which in turn are compromised by slow speed of processing. We propose, therefore, that antidepressant non-response in older adults with PS deficits is caused by expectancy failure and that targeting PS deficits prior to antidepressant treatment will restore the capacity to form expectations thereby improving antidepressant treatment response. An excellent candidate for improving PS is computerized cognitive training (CCT), i.e., exercises that target, train, and strengthen specific cognitive processes with the use of structured drills and repeated practice. To test our expectancy-processing speed model, 100 depressed adults age 60 and over with PS deficits will be recruited. Participants will be randomized to either CCT or control (Solitaire) for 4 weeks. Both conditions will train for 25 minutes per day, 7 days per week. At the conclusion of this four-week period, patients will be randomly assigned to high versus low expectancy treatment conditions. Patients assigned to the low expectancy condition will be told they will receive either placebo or escitalopram when in fact they will receive escitalopram for eight weeks. Patients assigned to the high expectancy condition will be told they will receive escitalopram for eight weeks. Neuropsychological assessment will occur at baseline and weeks 4 and 12 whereas MRI scans will be conducted at baseline and week 4. Clinical assessments will be conducted biweekly throughout the study. The goals of this study are to 1) To determine whether PS mediates the relationship between CCT and expectancy, and 2) To compare endpoint depression scores as a function of CCT and expectancy conditions. The novel experimental therapeutics approach taken in this proposal cuts across several research themes (prevention and translation) and addresses many of the challenges (digital technology and neural circuits) elaborated in NIMH’s Strategic Plan for mental health research in the 22st century. Consistent with NIMH goals, it also develops strategies for tailoring existing interventions to optimize outcomes and elucidates the mechanism by which antidepressant treatment in LLD can be restored.

项目摘要：主要抑郁症（MDD）是残疾，发病率和 在整个生命周期中的死亡率，并在后期构成了一个特别严重的公共卫生问题。晚年抑郁症 （LLD）是高度复发的，可能会变得慢性，并且通常很难治疗。抗抑郁药通常是 由于存在神经认知因素，包括加工速度缓慢，因此在该人群中无效 （PS），执行功能障碍（ED）和脑血管疾病（CVD）干扰治疗。这是至关重要的， 因此，我们制定了解决抗抑郁药无反应的干预措施，并显着改善了 数百万弱势老年人的生活质量。我们最近确定，非 - 该人群的反应是预期效应受损的，进而被慢速损害 加工。因此，我们建议在具有PS定义的老年人的抗抑郁药无反应是引起的 根据预期失败，靶向PS在抗抑郁治疗前定义将恢复能力 形成期望，从而改善抗抑郁治疗反应。改进的出色候选人 PS是计算机化认知培训（CCT），即针对特定认知的练习 使用结构化演习和重复实践的过程。测试我们的期望处理速度 将招募60岁及60岁以上的100个抑郁症成年人。参与者将是随机的 进行CCT或对照（纸牌）4周。两种情况都将每天训练25分钟，每周7天。 在这个四周期间的结论中，将随机分配到高期望与低期望 治疗条件。分配到低期望条件的患者将被告知他们将收到任何 安慰剂或依他普兰实际上他们会收到依他张兰氏症八周。分配给 高期待状态将被告知他们将在八个星期内接受依源抗拉氏症。神经心理学 评估将在基线和第4周和第12周进行，而MRI扫描将在基线和 第4周。在整个研究中每两周进行临床评估。这项研究的目标是1） 确定PS是否介导CCT和期望之间的关系，以及2）比较端点 抑郁症得分是CCT和预期条件的函数。新型实验疗法 该提案削减了几个研究主题（预防和翻译）和地址的方法 NIMH的精神战略计划中阐述了许多挑战（数字技术和神经回路） 22世纪的健康研究。与NIMH目标一致，它还制定了定制现有的策略 干预措施以优化结果并阐明在LLD中抗抑郁治疗的机制 恢复。