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.

这项更新申请建立在R01 NIH福格蒂国际中心支持的我们目前的研究基础上