Targeting Processing Speed Deficits to Improve Social Functioning and Lower Psychosis Risk in Adolescents at Clinical High Risk for Psychosis

针对处理速度缺陷，改善临床精神病高风险青少年的社会功能并降低精神病风险

• 批准号: 10193909
• 负责人: BARBARA A. CORNBLATT
• 金额: $ 53.9万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10193909
• 关键词: 20 year old; Adolescent; Adolescent and Young Adult; Adopted; Adult; Aftercare; Age; Antipsychotic Agents; Architecture; Attenuated; Behavior; Brain; Child; Clinical; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Consensus; Data; Disease; Distal; Dose; Dropout; Early Intervention; Environment; Etiology; Exercise; Future; Hour; Impairment; Individual; Internet; Intervention; Lead; Measurement; Measures; Mental disorders; Modeling; Motivation; National Institute of Mental Health; Neurocognitive; Neuropsychology; Noise; Outcome; Outcome Measure; Participant; Patients; Performance; Pharmacology; Phase; Pilot Projects; Prevention; Prevention Research; Preventive; Psychoses; Psychotic Disorders; Randomized; Reporting; Research; Resistance; Risk; Running; Sampling; Schizophrenia; Signal Transduction; Social Functioning; Social Interaction; Speed; Structure; Support Groups; Symptoms; Teenagers; Testing; Thinking; Time; Training; Youth; active control; arm; base; clinical heterogeneity; cognitive change; cognitive system; cognitive training; computer game; computerized data processing; design; high risk; high-risk adolescents; improved; improved outcome; information processing; innovation; interest; novel; novel strategies; processing speed; psychosocial; remote delivery; schizophrenia risk; study population; treatment research

Project Summary Prevention of schizophrenia has primarily focused on adolescents and young adults who are considered to be at clinical high risk (CHR) for psychosis. These youngsters display subtle clinical symptoms that are similar to psychosis but not as intense, and therefore considered to still be amenable to early intervention. Initial prevention efforts used anti-psychotics as the primary preventive agents but these were shown to be largely ineffective. More recent approaches have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness in CHR adolescents. However, while cognitive remediation has shown substantial promise for improving cognitive deficits and improving outcomes in patients with schizophrenia, it has not yet been markedly successful with CHR youth. The proposed study will test an innovative internet- based remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention for CHR adolescents ages 14-20 years old that targets early processing speed deficits as measured at the neuropsychological level with the processing speed domain from the NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery. The proposed SCORES treatment package is grounded in a theoretical framework, supported by findings from our group and others, where processing speed deficits contribute to poor social functioning, which in turn leads to an increased risk for psychosis. We specifically selected cognitive remediation because it directly targets a core cognitive mechanism, processing speed, which is a rate limiting factor to higher order behaviors and clinical outcome in CHR adolescents. To overcome past difficulties in applying a cognitive remediation treatment to CHR teenagers, we have developed a platform to support our targeted processing speed training, which involves reducing the heterogeneity of the CHR study population (including a reduced age range, narrowed clinical criteria, and targeting individuals with pre-existing processing deficits). In addition, we have adding a novel support surround component which is expected to increase enjoyment and promote retention. In the single-arm R61 phase, a 2-year proof of concept study, 30 CHR individuals will receive SCORES for 10 weeks(4hrs per wk/40 hrs total) with a midpoint assessment at 20 hours (5 weeks) to demonstrate target engagement and identify the optimal dose of SCORES needed to engage the target. In the R33 phase, a 3 year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR individuals randomized to SCORES (optimized dose)or to a Video GameControl condition to firmly establish the centrality of processing speed. In addition, the R33 phase will determine if changes in target engagement are associated with improved social functioning and decreasing attenuated positive symptoms.

项目概要 精神分裂症的预防主要集中于青少年和年轻人，他们被认为是 处于精神病临床高风险（CHR）。这些年轻人表现出微妙的临床症状，类似于 精神病，但不那么严重，因此被认为仍然适合早期干预。最初的 预防工作使用抗精神病药物作为主要预防药物，但这些药物被证明在很大程度上是 无效。最近的方法侧重于纠正容易发生的认知缺陷 CHR 青少年未来疾病的明显和预测。然而，虽然认知矫正已表明 它对于改善精神分裂症患者的认知缺陷和改善结果具有重大前景 在 CHR 青年方面尚未取得显着成功。拟议的研究将测试创新的互联网 针对 CHR 的远程特定认知矫正加周围（或 SCORES）干预 14-20 岁的青少年，目标是解决早期处理速度缺陷（按照在 NIMH 测量和治疗处理速度域的神经心理学水平 改善精神分裂症认知的研究（MATRICS）共识认知电池。拟议的 SCORES 治疗方案以理论框架为基础，并得到我们小组的研究结果和 在其他情况下，处理速度不足会导致社会功能不佳，进而导致 精神病的风险增加。我们特别选择认知矫正，因为它直接针对核心 认知机制、处理速度，这是高阶行为和临床的速率限制因素 CHR 青少年的结果。克服过去在应用认知矫正治疗时遇到的困难 CHR青少年，我们开发了一个平台来支持我们有针对性的处理速度训练，这 涉及减少 CHR 研究人群的异质性（包括缩小年龄范围、缩小 临床标准，并针对预先存在处理缺陷的个体）。此外，我们还添加了一个 新颖的支撑环绕组件有望增加乐趣并促进保留。在 单臂 R61 阶段，为期 2 年的概念验证研究，30 名 CHR 个人将获得 10 分的分数 周（每周 4 小时/总共 40 小时），并在 20 小时（5 周）进行中点评估以证明目标 参与并确定参与目标所需的最佳 SCORES 剂量。在R33阶段，3 年试点研究，我们将在 54 名 CHR 个体的新样本中复制目标参与度 随机分配到分数（优化剂量）或视频游戏控制条件以牢固建立中心性 的处理速度。此外，R33 阶段将确定目标参与度的变化是否相关 随着社会功能的改善和减弱的阳性症状的减少。