Identifying mechanisms of response to therapeutic intervention in clinical high risk (CHR) for psychosis: a bridge to treatment

确定精神病临床高危（CHR）治疗干预的反应机制：治疗的桥梁

• 批准号: 10538935
• 负责人: Huijun Li
• 金额: $ 64.68万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10538935
• 关键词: Achievement; Address; Biological Markers; Brain; China; Chinese; Clinical; Clinical Trials; Cognition; Collaborations; Data; Development; Effectiveness of Interventions; Fogarty International Center; Follow-Up Studies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Grant; Individual; Institution; Intervention; Knowledge; Light; Link; Literature; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Methods; Modeling; Neurocognitive; Neuronal Plasticity; Neuropsychology; Outcome; Persons; Prognosis; Protocols documentation; Psychoses; Research; Rest; Role; Schizophrenia; Short-Term Memory; Site; Symptoms; Techniques; Testing; Therapeutic; Therapeutic Intervention; Time; Training; United States National Institutes of Health; Vulnerable Populations; Work; adverse outcome; allostasis; base; clinical high risk for psychosis; clinical investigation; clinical predictors; clinically relevant; early psychosis; high risk; high risk population; individual variation; insight; intervention effect; longitudinal analysis; mental health center; mindfulness meditation; neurofeedback; neuroregulation; novel; novel marker; post intervention; prevent; primary outcome; programs; psychobiologic; psychosis risk; relating to nervous system; repetitive transcranial magnetic stimulation; response; response biomarker; tool

This renewal application builds upon our current study supported by the R01 NIH Fogarty International Center grant, entitled “Psychobiological Follow-up Study of Transition from Prodrome to Early Psychosis” (R01MH111448). This proposal focuses on two persistent needs in clinical high risk (CHR) research: 1) the identification of novel biomarkers associated with transition to psychosis and other functional and clinical outcomes; and 2) the identification of symptom-specific brain circuit targets that can be engaged in future clinical trials. We hypothesize that clinically relevant biomarkers for individual-specific prognosis in CHR will be enhanced by the inclusion of measures that capitalize on the quantitative assessment of neural plasticity and are likely amenable to change. In this view, CHR outcomes are likely determined by both pathophysiology and by the brain’s capacity to adapt and respond to pathophysiology via neural plasticity mechanisms (i.e., allostasis). We thus propose to examine brain circuit plasticity biomarkers relevant to CHR by administering non-invasive neuromodulation via two novel paradigms that, as we have demonstrated, engage brain networks involved in negative and positive symptoms in schizophrenia. These two neuromodulation techniques are: 1. repetitive transcranial magnetic stimulation (rTMS)1 and 2. real time fMRI neurofeedback enhanced mindful meditation (mb-rt-fMRI-NFB)2. We will collect both traditional biomarkers (clinical, neuropsychological, ERP, MRI, DTI and resting state MRI) as well as novel allostatic biomarkers (i.e., biomarkers that quantify neural changes pre- relative to post-intervention). These two interventions, which have not been used with CHR subjects before, will be tested in 200 CHR (50 CHR per experimental condition) and 100 HC over 5 years. Furthermore, we will continue to enhance knowledge capacity at the Shanghai Mental Health Center (SMHC), where our Chinese collaborators are based. We will also examine the effectiveness of these interventions in CHR as a bridge to future therapeutic treatments (Aims 1 and 2), and we will test traditional and allostatic biomarkers as predictors of clinical and neurocognitive outcomes (Aim 3). Additionally, we will significantly enhance research capacity by building on already established achievements and collaborations, and by extending our reach to new institutions (Aim 4). This competitive renewal capitalizes on a unique set of strengths at a single site (SMHC) and on a collaboration with the Shanghai research team, which has proven to be most productive in the current grant cycle. We believe that this highly novel study will contribute to the development of future therapeutic interventions in CHR, which will prevent this vulnerable population from developing adverse outcomes and, at the same time, will enrich the CHR field with new insights into the pathophysiology of this condition.

此更新申请以我们目前由 R01 NIH Fogarty 国际中心支持的研究为基础 赠款，题为“从前驱症状到早期精神病转变的心理生物学随访研究” （R01MH111448）。该提案重点关注临床高风险（CHR）研究中的两个持续需求：1） 鉴定与转变为精神病以及其他功能和临床相关的新型生物标志物 结果；2) 识别可用于未来临床的症状特异性脑回路目标 我们认为 CHR 个体特异性预后的临床相关生物标志物将是 通过纳入利用神经可塑性定量评估的措施来加强 从这种观点来看，CHR 结果可能是由病理生理学和病理生理学共同决定的。 通过大脑通过神经可塑性机制（即动态平衡）适应和响应病理生理学的能力。 因此，我们建议通过施用非侵入性方法来检查与 CHR 相关的脑回路可塑性生物标志物。 通过两本小说进行神经调节，正如我们已经证明的范式，使大脑网络参与 精神分裂症的阴性和阳性症状这两种神经调节技术是： 1. 重复性。 经颅磁刺激 (rTMS)1 和 2. 实时功能磁共振成像神经反馈增强正念冥想 (mb-rt-fMRI-NFB)2 我们将收集传统生物标志物（临床、神经心理学、ERP、MRI、DTI 和 静息态 MRI）以及新型变稳态生物标志物（即量化神经变化前的生物标志物） 相对于干预后），这两种干预措施以前未曾在 CHR 受试者中使用过。 在 5 年内，我们将在 200 CHR（每个实验条件 50 CHR）和 100 HC 中进行测试。 继续提高上海精神卫生中心 (SMHC) 的知识能力，我们的中国人在这里 我们还将检查这些干预措施在 CHR 中作为桥梁的有效性。 未来的治疗方法（目标 1 和 2），我们将测试传统和变态生物标志物作为预测因子 此外，我们将通过以下方式显着提高研究能力： 以已经取得的成就和合作为基础，并将我们的影响力扩展到新的机构 （目标 4）这种竞争性更新利用了单个站点 (SMHC) 和一个独特的优势。 与上海研究团队的合作，已被证明在当前的资助中是最富有成效的 我们相信这项高度新颖的研究将有助于未来治疗干预措施的发展。 在 CHR 中，这将防止这一弱势群体产生不良后果，同时， 将为CHR领域提供对该疾病病理生理学的新见解。