Neurodevelopment of Mesolimbic Afferents in Healthy Adolescents and First-Episode Psychosis

健康青少年和首发精神病中脑边缘传入神经发育

• 批准号: 9542387
• 负责人: Vishnu Pradeep Murty
• 金额: $ 16.57万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-09 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9542387
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Age; Age-Years; Animal Model; Antipsychotic Agents; Award; Behavior; Biological Assay; Caregivers; Chronic; Clinical; Communities; Data Analyses; Deterioration; Development; Diffusion; Disease; Dopamine; Economics; Emotional; Etiology; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Grant; Hippocampus (Brain); Human; Individual; Intervention; Investigation; K-Series Research Career Programs; Knowledge; Learning; Measures; Medial; Mediating; Mentors; Modeling; Nature; Participant; Pathology; Pathway Analysis; Patients; Pharmaceutical Preparations; Phase; Play; Population; Positron-Emission Tomography; Prefrontal Cortex; Psychopathology; Psychotic Disorders; Regulation; Research; Research Domain Criteria; Research Training; Rest; Rewards; Risk; Role; Sampling; Schizophrenia; Signal Transduction; Substantia nigra structure; System; Systems Development; Techniques; Testing; Time; Training; Translating; Translations; Universities; Ventral Tegmental Area; Visit; Work; base; clinical predictors; cognitive neuroscience; data archive; dopamine system; dopaminergic neuron; emerging adult; first episode psychosis; follow-up; insight; lens; mesolimbic system; multimodality; neurodevelopment; neuroimaging; neuroimaging marker; neuroregulation; novel; phenomenological models; programs; recruit; relating to nervous system; remediation; social; spectrograph; translational neuroscience; white matter; young adult

Project Summary/Abstract The objective of this Career Development Award is to support new mentored training in cognitive neuroscience studies of dopamine-related function in healthy adolescents and first-episode psychosis, as the candidate begins an independent research program. Psychosis is a devastating illness that afflicts ~3% of the world’s population, and has sever economic and social/emotional consequences for both patients and their caregivers. Prior research has implicated deficits in dopamine systems in both the etiology and pathology of the disorder, and thus remediation of this system has been a prominent target for intervention. Although these deficits have been well documented, open questions remains as to how and why these deficits emerge. Prominent models of psychosis have implicated aberrant development of neural systems regulating the activation of dopamine systems. However, very little research has investigated how these regulatory systems develop in normative populations; let alone how deviations from normative development may be implicated in psychosis. Thus, a full understanding of psychosis necessitates a characterization of dopamine-related networks in healthy adolescence and deviations from these trajectories in psychosis. These findings will provide insight into determinants of risk for conversion from a developmental perspective and in turn the timing of interventions. The proposed award will build upon the candidate’s prior training in cognitive neuroscience, to extend this knowledge into the domain of normative development in adolescents and aberrant development in psychosis within dopamine-related networks. Aim 1 will investigate the normative development of neural systems regulating engagement of the ventral tegmental area and substantia nigra, the core of the mesolimbic dopamine system, using multimodal neuroimaging. These developmental neuroimaging markers will then be associated with direct and indirect measures of dopamine to assess how they relate to dopaminergic function. Aim 2 will evaluate how individuals with first-episode psychosis deviate from the normative trajectories characterized in Aim 1, and further probe how these deviations relate to anti-psychotic medication status. Finally, Aim 3 will have first-episode patients return for a 2-year follow-up to characterize how the clinical course of psychosis relates to early markers of dopamine-related dysfunction. Mentored training will compliment the candidate’s expertise in neuroimaging of dopamine-related circuits in healthy adults. Paralleling the proposed research, training will focus on the candidate gaining expertise in conducting neuroimaging studies in adolescent (Aim 1) and psychosis populations (Aim 2,3). Further, the candidate will gain expertise in the translation of animal models of behavior in adolescent and psychosis population, with a focus on understanding the nature of homology across multiple species (Aims 1-3). Finally, the candidate will gain expertise in experimental techniques associated with studying neurodevelopment (e.g., longitudinal data analysis; Aims 1-3), psychosis (e.g., adjustment for antipsychotic medication, characterizing clinical phenomenology; Aims 2-3), and translational neuroscience (e.g., integration of direct/indirect measures of dopamine; Aim 3). The candidate has recruited a mentoring team with expertise in all of the above domains led by mentor Dr. Bea Luna, an expert in adolescent development, and co-mentor Deanna Barch, an expert in neuroimaging in psychosis populations. Further, the candidate will take advantage of the known strengths of the schizophrenia and adolescent research communities, as well as the emphasis on cross-species translation at the University of Pittsburgh. The proposed research will offer novel insight into dopamine dysfunction in psychosis through the lens of adolescent neurodevelopment. Further, the training will lay the foundation for an independent research program assaying the neurodevelopmental of neuromodulatory systems in psychosis. !

项目摘要/摘要 该职业发展奖的目的是支持认知神经科学领域的新修订培训 在健康青少年和第一集精神病中，多巴胺相关的功能作为候选人 开始一个独立的研究计划。精神病是一种毁灭性的疾病，遭受了世界上约3％ 人口，并对患者及其护理人员产生了几种经济和社会/情感上的后果。 先前的研究已经在多巴胺系统的病因和病理学中实施了定义， 因此，对该系统的修复一直是干预的重要目标。尽管这些定义有 有充分的文献记载，关于如何以及为什么这些定义出现的开放问题。突出的模型 精神病已经实施了对多巴胺激活的神经系统的异常发展 系统。但是，很少的研究研究了这些监管系统如何在正常中发展 人口；更不用说与正常发展的偏离可能与精神病有关。那，一个完整的 了解精神病必要的是健康中与多巴胺相关网络的表征 青少年和偏离精神病中的这些轨迹。这些发现将提供有关 从发展的角度和干预措施的时间安排转换风险的决定因素。 拟议的奖项将基于候选人的认知神经科学培训，以扩展 这些知识进入青少年正常发展领域的知识和异常发展 多巴胺相关网络中的精神病。 AIM 1将研究神经的正常发展 腹侧对段区域和底底尼格拉（Mesolimbic的核心 多巴胺系统，使用多模式神经影像学。这些发展性神经影像标记将是 与多巴胺的直接和间接度量相关，以评估它们与多巴胺能功能的关系。 AIM 2将评估第一集精神病患者如何偏离规范轨迹 在AIM 1中进行了特征，并进一步探究了这些离职与抗精神药物状况的关系。 最后，AIM 3将使第一集患者返回2年的随访，以表征临床的方式 与多巴胺相关功能障碍的早期标记有关的精神病病程。指导的培训意志 赞美候选人在健康成年人中与多巴胺相关电路神经影像学方面的专业知识。 与拟议的研究并行，培训将集中于候选人获得专业知识 青少年（AIM 1）和精神病人群（AIM 2,3）的神经影像学研究。此外，候选人将 在青少年和精神病人群中的动物行为模型的翻译中获得专业知识， 专注于理解多种物种的同源性的性质（目标1-3）。最后，候选人将 获得与研究神经发育相关的实验技术的专业知识（例如，纵向数据 分析; AIMS 1-3），精神病（例如，抗精神病药的调整，临床表征 现象学；目标2-3）和转化神经科学（例如，直接/间接测量的集成 多巴胺；目标3）。候选人已招募了一支在上述所有领域中具有专业知识的心理团队 撰写于青少年发展专家Bea Luna博士，以及同事Deanna Barch，专家 精神病群体的神经影像学。此外，候选人将利用已知的优势 精神分裂症和青少年研究社区，以及对跨物种翻译的重视 在匹兹堡大学。拟议的研究将为多巴胺功能障碍提供新颖的见解 通过青春期神经发育镜头的精神病。此外，培训将为 独立研究计划，分析了精神病中神经调节系统神经发育。 呢