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.

项目概述：重度抑郁症（MDD）是导致残疾、发病和死亡的主要原因