What the Nose Knows: Hedonic Capacity, Psychosocial Interventions and Outcomes in Schizophrenia

鼻子知道什么：精神分裂症的享乐能力、社会心理干预和结果

• 批准号: 10612488
• 负责人: Raquelle Mesholam-Gately
• 金额: $ 15.13万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612488
• 关键词: Address; Adult; Age; Antipsychotic Agents; Attention; Award; Behavior; Behavioral; Brain; Clinical; Clinical Trials; Clozapine; Cognition; Cognitive; Cognitive deficits; Communities; Data; Development; Effectiveness; Emotional; Enrollment; Functional disorder; Funding; Guidelines; Heterogeneity; Impairment; Individual; Intervention; Investigation; Knowledge; Learning; Literature; Measurement; Measures; Motivation; National Institute of Mental Health; Neurocognitive; Nose; Odors; Olfactory Pathways; Outcome; Outcome Measure; Outpatients; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pilot Projects; Predisposition; Process; Psychological reinforcement; Psychoses; Public Health; Questionnaires; Research; Research Domain Criteria; Rewards; Role; Sampling; Schizophrenia; Site; Social Functioning; Social Interaction; Social outcome; Standardization; Supportive care; Symptoms; System; Testing; Therapy Clinical Trials; Time; Variant; cognitive enhancement; cognitive function; comparison control; cost; effective intervention; evidence base; experience; functional disability; functional outcomes; hedonic; improved; improved outcome; indexing; information gathering; innovation; neural; neuroimaging; novel; novel strategies; novel therapeutic intervention; olfactory stimulus; pleasure; psychosocial; psychosocial rehabilitation; psychotic symptoms; public health relevance; randomized, clinical trials; recruit; reward circuitry; skills training; social cognition; social skills; treatment effect

Modified Project Summary/Abstract Section While psychotic symptoms are the most florid manifestations of schizophrenia, impairments in social and cognitive functioning are the most disabling features, and represent critical targets for intervention. Cognitive Enhancement Therapy (CET) and Social Skills Training (SST) are established, evidence-based psychosocial interventions that target functional disability in schizophrenia, but outcomes can be heterogeneous. The potential important contribution of the brain’s reward system functioning to the heterogeneity of these effects has yet to be examined. The role of reward circuitry in the cognitive, emotional and behavioral deficits of schizophrenia has garnered increasing attention in recent years, particularly given the critical relationship of reward to learning and social interactions, and the substantial public health importance of its potential association with better functional outcomes. While there are several measures of reward processes, a growing number of studies have used the olfactory system to characterize the neural substrate of the reward system and probe hedonic capacity across the psychosis spectrum. This includes preliminary findings, in people with schizophrenia, that olfactory hedonic capacity (OHC; range of hedonic ratings between pleasant and unpleasant odors) is reduced, though not in those treated with clozapine, and that OHC moderates neurocognitive outcomes in a CET clinical trial. Additionally, these olfactory assessments have the advantages of low test burden in terms of time, tolerability, cost and ease of administration, along with strong reliability and less susceptibility to state-dependent variation than questionnaires and some behavioral indices. As such, to address heterogeneous treatment effects and strive to improve outcomes, this novel project proposes the first investigation of OHC as a moderator of CET and SST effectiveness with special attention to the relationship to other indices of reward and to the role of medication. One hundred-sixteen adults with schizophrenia will be recruited from a large, 19-site, randomized clinical trial of CET vs. SST in schizophrenia, with comparable enrollment between the treatments, and assessments at baseline, 6, and 12 months (end of intervention). Moderator analyses will evaluate the predictive effects of OHC on CET and SST outcomes of community functioning, neuro- and social cognition, and social skills. The relationship between OHC and other indices of reward and clinical symptoms will also be analyzed, as will the potential interaction between medication (clozapine vs. other) and OHC on outcomes. The preliminary data from this project are expected to inform a highly promising line of research that is critical for advancing the treatment of functional impairment in schizophrenia. In examining the predictive utility of OHC measurement for targeted psychosocial rehabilitation, this projects aligns with: a). R21 guidelines emphasizing novelty and innovation, b). RDoC principles of providing mechanistic knowledge about which individuals are most likely to benefit from these interventions, and c). NIMH strategic objectives to facilitate the tailoring of existing interventions and development of new approaches to optimize outcomes for people with schizophrenia.

修改项目摘要/摘要部分 虽然精神病性症状是精神分裂症最明显的表现，但社会和认知功能障碍是最具致残性的特征，并代表了干预的关键目标。认知增强疗法（CET）和社会技能训练（SST）是建立在循证基础上的心理社会干预措施，针对精神分裂症的功能障碍，但结果可能是异质的。大脑的奖励系统功能对这些效应的异质性的潜在重要贡献还有待研究。近年来，奖励回路在精神分裂症的认知、情感和行为缺陷中的作用越来越受到关注，特别是考虑到奖励与学习和社会互动的关键关系，以及其与更好的功能结果的潜在关联在公共卫生方面的重要性。虽然奖励过程有几种测量方法，但越来越多的研究使用嗅觉系统来表征奖励系统的神经基质，并在精神病谱系中探索享乐能力。这包括初步发现，在精神分裂症患者中，嗅觉享乐能力（OHC;愉快和不愉快气味之间的享乐评级范围）降低，但不是在那些接受氯氮平治疗的人中，OHC在CET临床试验中调节神经认知结果。此外，这些嗅觉评估在时间、耐受性、成本和易于管理方面具有低测试负担的优点，沿着有较强的可靠性，并且与问卷和一些行为指标相比对状态依赖性变化的敏感性较低。因此，为了解决异质性治疗效果并努力改善结局，该新项目首次提出将OHC作为CET和SST有效性的调节剂进行研究，特别关注与其他奖励指数的关系以及药物的作用。将从一项大型、19个中心、随机临床试验中招募116名精神分裂症成人患者，比较CET与SST治疗精神分裂症，两种治疗的入组情况以及基线、6个月和12个月（干预结束）时的评估结果相当。主持人分析将评估OHC对CET和SST结果的预测作用，包括社区功能、神经和社会认知以及社交技能。还将分析OHC与其他奖励指数和临床症状之间的关系，以及药物（氯氮平与其他药物）与OHC对结局的潜在相互作用。该项目的初步数据预计将为一系列非常有前途的研究提供信息，这些研究对于推进精神分裂症功能障碍的治疗至关重要。在检查OHC测量对有针对性的心理社会康复的预测效用时，该项目符合：a）。R21指南强调新奇和创新，B）。RDoC原则，提供关于哪些个体最有可能从这些干预措施中受益的机械知识，以及c）。NIMH的战略目标是促进现有干预措施的定制和新方法的开发，以优化精神分裂症患者的结局。