Predictive Markers and Mechanisms of Persistent Psychotic-like Experiences in Children: An Adolescent Brain and Cognitive Development Study Analysis

项目名称 青少年持续性精神病样经历的预测标志和机制 脑与认知发展研究分析 项目摘要/摘要 我的长期职业目标是建立一个非常有影响力和独立的研究项目，成为一名 计算精神病学的广谱领导者和创新者。因此，我提出以下培训目标： 1)获得计算精神病学方法和统计学方面的正式培训，包括深度培训 学习和结构方程建模，2)加深对该领域的理解 发展精神病理学，以及3)获得发展和维持独立的 拥有自己的实验室的调查员职位。为了实现第一个目标，我将定期与加州大学 加州大学戴维斯分校(UCD)教员共同导师伊恩·戴维森和埃米利奥·费雷尔，参加相关的UCD课程，以及 完成以下具体目标的研究计划：1)利用青少年大脑的深度学习和 认知发展(ABCD)研究数据(人口统计/临床信息、神经认知测试、 神经成像数据和环境指标)，预测儿童精神病样经历(PLE)痛苦评分 第二年(即，预测第一年PQ-BC困境的基线数据，预测第二年的第一年数据 遇险等)，以及2)使用来自深度学习的基于规则的指导，使用可解释的人工智能(XAI)算法，使用 潜在轮廓(即，纵向轨迹，例如，出现的轨迹， 缺少、反复、坚持)检验关于纵向机制的假设(S)，这可能导致 ABCD队列中的持久PLE。在目标1中，将使用XAI方法来识别深层所使用的规则 学习者进行决策；在目标2中，这些规则随后将用于创建用于建模配置文件的潜在结构 纵向轨迹。如果目标1中的每一次迭代分析都一致地达到R2&>0.80，则表明 ABCD仪器可以在测量一年后在潜在的临床可实施的情况下预测PLE的严重程度 达到并帮助生成旨在降低持续性风险的个性化干预的未来假设 满心苦恼。对于目标2，将获得关于大脑结构、大脑功能、神经认知 能力和环境影响相互作用，影响PLE表达的时间进程。为了满足 第二个目标，我将接受指导，包括通过每月与合作导师Ellen博士的会议进行指导阅读 专门从事发展研究的世界著名精神病学家、NIMH科长莱本鲁夫特说。 我还将参加UCD提供的发展课程、研讨会和工作坊。为了实现第三个目标，我 我将每周与导师卡梅隆·卡特博士会面，我将从他那里获得最重要的职业指导。 这将包括学习如何创建和监督一个实验室，获得对社会的推荐 会员资格、获得网络机会、获得赠款赞助和接受RCR相关 指导。我还将参加UCD提供的指导和恩赐技能研讨会，参加校外 工作坊提供实践活动，提供基本的管理技能，完成 正式的UCD RCR计划，并通过为研究助理和博士后提供建议来获得指导经验。

PROJECT TITLE Predictive Markers and Mechanisms of Persistent Psychotic-like Experiences in Children: An Adolescent Brain and Cognitive Development Study Analysis PROJECT SUMMARY/ABSTRACT My long-term career goal is to establish a highly influential and independent research program and become a broad spectrum leader and innovator in computational psychiatry. I therefore propose the following training goals: 1) To gain formalized training in computational psychiatry methods and statistics, including deep learning and structural equation modeling, 2) to obtain a deeper understanding of the field of developmental psychopathology, and 3) to acquire training in developing and sustaining an independent investigator position with his own laboratory. To meet the first goal, I will meet regularly with University of California Davis (UCD) faculty co-mentors Ian Davidson and Emilio Ferrer, attend relevant UCD classes, and complete a Research Plan with the following Specific Aims: 1) Using deep learning from Adolescent Brain and Cognitive Development (ABCD) Study data (demographic/clinical information, neurocognitive testing, neuroimaging data, and environmental metrics), predict child psychotic-like experience (PLE) distress scores the following year (i.e., baseline data predicting year one PQ-BC distress, year one data predicting year two distress, etc.), and 2) Using rules-based guidance from deep learning using explainable AI (XAI) algorithms, use sequential, structural equation modeling (SEM) of latent profiles (i.e., longitudinal trajectories, e.g., emerging, absent, remitting, persistent) to test hypotheses regarding the longitudinal mechanism(s) which may lead to persistent PLEs in the ABCD cohort. In Aim 1, XAI methods will be used identify the rules used by the deep learner to make decisions; in Aim 2, these rules will then be used to create latent constructs for modeling profiles of longitudinal trajectories. If r2>0.80 is consistently achieved for each iterative analysis in Aim 1, it suggests that ABCD instruments may predict PLE severity one year after measurement at a potentially clinically implementable level and help generate future hypotheses for personalized interventions aimed at reducing risk for persistent PLE distress. For Aim 2, insight will be gained with regard to how brain structure, brain function, neurocognitive ability, and environmental influences interact to influence the time course of PLE expression. To meet the second goal, I will receive mentoring including guided readings via monthly meetings with co-mentor Dr. Ellen Leibenluft, a world-renowned psychiatrist specializing in developmental research and Section Chief at the NIMH. I will also attend developmental classes, seminars, and workshops offered by UCD. To meet the third goal, I will attend weekly meetings with mentor Dr. Cameron Carter, from whom I will gain overarching career guidance. This will include learning how to create and oversee a laboratory, obtaining recommendations for society memberships, acquiring networking opportunities, securing grant sponsorships, and receiving RCR-related guidance. I will also attend mentoring and grantsmanship workshops offered by UCD, attend an off-campus workshop providing hands-on activities to provide exposure to fundamental management skills, complete a formalized UCD RCR plan, and gain mentoring experience by advising a research assistant and postdoc.