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.

此续签申请基于我们当前的研究，由R01 NIH Fogarty International Center支持 格兰特（Grant （R01MH111448）。该提案侧重于临床高风险（CHR）研究的两个持续需求：1） 鉴定与过渡到精神病以及其他功能和临床的新型生物标志物 结果； 2）识别症状特异性脑电路靶标，可以参与以后的临床 试验。我们假设CHR中个人特异性预后的临床相关生物标志物将是 通过包括利用神经可塑性定量评估的措施来增强 可能可以改变。从这种角度来看，CHR结果可能取决于病理生理学和 通过大脑通过神经可塑性机制（即Allostasis）适应和应对病理生理学的能力。 因此，我们建议通过管理非侵入性检查与CHR相关的脑电路可塑性生物标志物 正如我们所证明的，通过两个新型范式进行神经调节 精神分裂症的阴性和阳性症状。这两种神经调节技术是：1。竞争性 trancranial磁刺激（RTMS）1和2。实时fMRI神经反馈增强了正念冥想 （MB-RT-FMRI-NFB）2。我们将收集传统的生物标志物（临床，神经心理学，ERP，MRI，DTI和DTI和 静止状态MRI）以及新型的同层生物标志物（即，量化神经变化的生物标志物 相对于干预后）。以前尚未与CHR受试者一起使用的这两种干预措施将 在200个CHR（每个实验条件50个CHR）和5年内进行100 HC进行测试。此外，我们会的 继续在上海心理健康中心（SMHC）上增强知识能力 合作者是基于的。我们还将研究CHR中这些干预措施的有效性 未来的治疗疗法（目标1和2），我们将测试传统和同层生物标志物作为预测因子 临床和神经认知结果（AIM 3）。此外，我们将通过 建立在已经建立的成就和合作的基础上，并通过将我们的影响力扩展到新机构 （目标4）。这种有竞争力的续约资本利用了单个站点（SMHC）的独特优势和 与上海研究团队合作，该团队在当前赠款中被证明是最有效的 循环。我们认为，这项高度新颖的研究将有助于未来的治疗干预措施的发展 在CHR中，这将防止这种脆弱的人群发展不良后果，同时， 将通过对这种疾病的病理生理学的新见解来丰富CHR领域。