Genomic Architecture of Functional Brain Networks in PTSD

创伤后应激障碍（PTSD）中功能性大脑网络的基因组结构

• 批准号: 10584246
• 负责人: MARK W LOGUE
• 金额: $ 68.71万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-06 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584246
• 关键词: Address; Africa; Architecture; Area; Asia; Attention; Australia; Award; Behavioral; Brain; Collaborations; Communication; Communities; Coupling; Data; Data Set; Decentralization; Development; Diagnosis; Diagnostic; Dimensions; Europe; Functional Magnetic Resonance Imaging; Funding; Future; Gene Expression; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genomics; Genotype; Goals; Heritability; Institution; International; Knowledge; Lateral; Letters; Link; Maps; Mental disorders; Methods; Modeling; Neurosciences; North America; Paper; Pathway interactions; Patients; Pattern; Peer Review; Phenotype; Post-Traumatic Stress Disorders; Process; Progress Reports; Publishing; Research; Research Personnel; Rest; Role; Sampling; Severities; Signal Transduction; Site; Structure; Surface; Symptoms; Testing; Thick; Trauma; analysis pipeline; cloud based; cohort; data framework; data infrastructure; data sharing; design; drug discovery; experience; genetic architecture; genome wide association study; high dimensionality; independent component analysis; innovation; instrument; network models; neural; neurogenetics; neuroimaging; outreach; precision medicine; psychological trauma; spatiotemporal; symptom cluster; targeted treatment; trauma exposure

ABSTRACT Our overarching goal is to investigate the genetic architecture of canonical functional resting-state networks (RSN) in PTSD. The disruption of several canonical RSNs including the default mode network (DMN), ventral attention network (VAN), and salience network (SN) are strongly implicated in posttraumatic stress disorder (PTSD). These RSN alterations are associated with specific symptom clusters of PTSD (e.g. intrusive re-experiencing symptoms). Canonical RSN connectivity and regional amplitude of BOLD signal, which are associated with PTSD and its symptom dimensions, constitute highly heritable phenotypes (h2 = 0.4 – 0.6) that exceed the heritability of task-based fMRI and the majority of structural neuroimaging phenotypes. A genetic vulnerability to developing PTSD following exposure to trauma has long been hypothesized and is now supported by evidence. Discovery of the genetic factors involved in brain communication and brain connectivity that contribute to PTSD may prove vital to new treatment breakthroughs. The coupling of brain connectivity with its genetic architecture, mapping the neurogenetic pathways of PTSD, and new knowledge of neural and genetic mechanisms will support precision-medicine guided drug discovery for managing mental illnesses that follow psychological trauma. Our aims are to 1: Investigate differences in the genetic architecture of functional connectomics associated with PTSD. 2: Investigate the role of PTSD on the relationship between the genetic architecture of brain structure and functional connectomics. 3: Investigate the effects of PTSD on the link between gene transcription architecture and functional connectomics. The coupling of cortical functional connectomics with its genetic architecture and its transcriptional architecture in relation to known disruptions of functional connectomics in PTSD may offer exciting opportunities to discover targeted therapies. Mapping the neurogenetic pathways of PTSD to the severity of PTSD symptoms will also be critical to the future design, development, and selection of yet undiscovered treatments. Knowledge of their unique neural and genetic mechanisms will be vital to precision-medicine guided drug discovery for managing mental illnesses that may follow psychological trauma.

抽象的 我们的总体目标是研究规范功能静止状态的遗传结构 PTSD中的网络（RSN）。包括默认模式网络在内的几个规范RSN的破坏 （DMN），腹注意网络（VAN）和显着网络（SN）与创伤后有关 应激障碍（PTSD）。这些RSN改变与PTSD的特定症状簇有关（例如 侵入性重新体验症状）。典型的RSN连接和大胆信号的区域放大器， 与PTSD及其症状维度相关的，构成高度可遗传的表型（H2 = 0.4 - 0.6）超过了基于任务的fMRI和大多数结构神经影像型的遗传力。一个 长期以来，长期以来一直认为，在暴露创伤后，遗传脆弱性发生了PTSD 得到证据的支持。发现与大脑通讯和大脑连通性有关的遗传因素 这对PTSD的贡献可能对新的治疗突破至关重要。大脑连通性的耦合 凭借其遗传结构，绘制PTSD的神经遗传途径以及神经元和新知识 遗传机制将支持精确中等医学指导的药物发现，以管理精神疾病 遵循心理创伤。我们的目标是1：研究功能遗传结构的差异 与PTSD相关的连接组学。 2：研究PTSD在通用之间关系的作用 大脑结构和功能连接组学的结构。 3：研究PTSD对链接的影响 在基因转录体系结构和功能连接组之间。皮质功能的耦合 与已知的破坏有关 PTSD中的功能连接组学可能会为发现目标疗法提供令人兴奋的机会。映射 PTSD对PTSD症状严重程度的神经遗传途径对于未来的设计也至关重要， 开发和选择未被发现的治疗方法。了解其独特的神经和遗传 机制对于精确中等医学指引导的药物发现至关重要，以管理可能 遵循心理创伤。