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

修改后的项目摘要/摘要部分 虽然精神病症状是精神分裂症最丰富的表现，但社会和认知功能障碍是最具致残性的特征，是干预的关键目标。认知增强疗法(CET)和社会技能训练(SST)是建立在循证心理社会干预基础上的，针对精神分裂症的功能障碍，但结果可能是不同的。大脑奖赏系统的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，奖赏回路在精神分裂症认知、情绪和行为缺陷中的作用引起了越来越多的关注，特别是考虑到奖赏与学习和社会互动的关键关系，以及它与更好的功能结果的潜在关联对公共卫生的重要意义。虽然有几种衡量奖励过程的方法，但越来越多的研究使用嗅觉系统来表征奖励系统的神经底物，并探索整个精神病谱系的享乐能力。这包括在精神分裂症患者中的初步发现，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，尽管在接受氯氮平治疗的人中不是这样，在CET临床试验中，OHC缓和了神经认知结果。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测试负担低的优点，而且与问卷和一些行为指标相比，可靠性强，对状态依赖变化的敏感性较低。因此，为了解决不同的治疗效果并努力改善结果，这个新的项目提出了首次调查OHC作为CET和SST有效性的调节因素，并特别关注与其他奖励指数的关系和药物的作用。116名成年精神分裂症患者将从一项关于CET和SST治疗精神分裂症的19个地点的大型随机临床试验中招募，在治疗和基线、6个月和12个月(干预结束)时的评估之间进行类似的登记。主持人分析将评估OHC对社区功能、神经和社会认知以及社会技能的CET和SST结果的预测效果。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)和OHC对结果的潜在相互作用。来自该项目的初步数据有望为一系列非常有希望的研究提供信息，这对推进精神分裂症功能障碍的治疗至关重要。在检验OHC测量对有针对性的心理社会康复的预测性效用方面，本项目与：a)一致。R21指南强调新颖性和创新性，b)。RDoC提供关于哪些个人最有可能从这些干预措施中受益的机械性知识的原则，以及c)。NIMH的战略目标，以促进现有干预措施的定制和开发新的方法，以优化精神分裂症患者的结果。

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.