Connectomes Related to Anxiety and Depression in Adolescents

该提案是为了响应NIH资助机会与人类疾病相关的连接组而提交的 (U01)并响应NIMH的优先/感兴趣的疾病领域情绪和焦虑障碍。这是一 马萨诸塞州总医院（MGH）、马萨诸塞州研究所的研究人员之间的合作努力 麻省理工学院（MIT），姆克林医院，波士顿大学和人类连接组项目（HCP）在 圣路易斯的华盛顿大学。我们认为，（1）最先进的MRI技术和 MGH Martinos生物医学成像中心的方法，（2）与HCP积极合作， 验证神经成像协调，（3）波士顿范围内的经验丰富的临床专家联盟 研究人员，和（4）跨焦虑和抑郁谱的跨诊断焦点可以提供高- 符合融资机会规范的高质量数据集。我们建议把重点放在一个领域， 巨大的临床需求和公共卫生意义：更好地了解青少年精神障碍。 我们将焦虑和抑郁作为影响多个传统领域许多青少年的疾病， 精神病诊断，与青少年和年轻人的两个主要死亡原因密切相关 成年人（自杀和药物滥用相关事故），据了解， 导致终生精神疾病的发展根源。我们的研究方法由两个指导 原则（1）严格遵守HCP协议，以便开发大规模、集成和不断增长的数据 科学界可用的集合，以及（2）与来自 NIMH研究领域标准项目（RDoC），具体而言：（a）“急性威胁/恐惧”结构， 与特定神经网络中的非典型结构和功能相关，特别是杏仁核、眶额 皮层（OFC）和腹内侧前额叶皮层（vmPFC）;以及（B）“奖励预测错误”构造， 它与眶额皮层、腹侧纹状体和中脑腹侧被盖区有关。四年来，我们 目的是（1）操作MRI数据收集和行为表征，协调和验证 与人类连接组计划（HCP）;（2）招募和表征临床和行为，225 年龄在14-15岁的青少年有和没有焦虑和/或抑郁（180例患者，45例对照）;和（3）进行 并与参与者一起分析HCP成像。我们假设杏仁核-眶额皮层的更大激活 回路将与更严重的恐惧测量分数相关，纹状体-OFC的激活较少 电路将与奖励错误预期的措施更严重的分数相关。我们亦会（a） 检查神经成像分析是否通过伪影检测工具和生理混叠得到增强 公开可用的并且可以与HCP整合的校正，以及（B）创建年龄特异性的 用于自动重建上述回路中涉及的白质束的人类束图谱和工具， 也将公开发布。

This proposal is submitted in response to NIH Funding Opportunity Connectome Related to Human Disease (U01) and in response to NIMH's priority/disease area of interest mood and anxiety disorders. This is a collaborative effort among researchers at the Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), McLean Hospital, Boston University, and the Human Connectome Project (HCP) at Washington University in St. Louis. We believe that the combination of (1) state-of-the art MRI technology and methods at the MGH Martinos Center for Biomedical Imaging, (2) an active collaboration with the HCP to validate neuroimaging harmonization, (3) a Boston-wide consortium of experienced and expert clinical researchers, and (4) a transdiagnostic focus across the anxiety and depression spectrum can deliver a high- quality dataset that meets the specification of the Funding Opportunity. We propose to focus on an area of great clinical need and public health implication: better understanding of psychiatric disorders in adolescence. We target anxiety and depression as diseases that affect many adolescents across multiple traditional psychiatric diagnoses, that are strongly associated with two leading causes of death in adolescents and young adults (suicide and substance-abuse related accidents), and that are understood to frequently have developmental roots leading to lifelong psychiatric disorders. Our research approach is guided by two principles (1) careful adherence to HCP protocols so as to develop large-scale, integrated, and growing data sets available to the scientific community, and (2) a research approach aligned with two constructs from the NIMH Research Domain Criteria Project (RDoC), specifically: (a) the “Acute Threat/Fear” construct, which is associated with atypical structure and function in specific neural networks, especially amygdala, orbitofrontal cortex (OFC), and ventral medial prefrontal cortex (vmPFC); and (b) the “Reward Prediction Error” construct, which is associated with OFC, ventral striatum, and the midbrain ventral tegmental area. Across four years we aim to (1) operationalize MRI data collection and behavioral characterization that is harmonized and validated with the Human Connectome Project (HCP); (2) recruit and characterize clinically and behaviorally, 225 adolescents ages 14-15 with and without anxiety and/or depression (180 patients, 45 controls); and (3) perform and analyze HCP imaging with participants. We hypothesize that greater activation in the amygdala-OFC circuit will correlate with more severe scores on measures of fear, and that lesser activation of the striatal-OFC circuit will correlate with more severe scores on measures of reward-error expectancy. We will also (a) examine whether neuroimaging analyses are enhanced with artifact-detection tools and physiological aliasing correction that are publicly available and could be integrated with the HCP, and (b) create an age-specific human tract atlas and tools for automated reconstruction of white-matter tracts involved in the above circuits, which will also be made publicly available.