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.

摘要 我们的首要目标是研究规范功能静息状态的遗传结构 创伤后应激障碍的网络(RSN)。包括默认模式网络在内的几个规范RSN的中断 (DMN)、腹侧注意网络(VAN)和突显网络(SN)与创伤后密切相关 应激障碍(PTSD)。这些RSN的改变与创伤后应激障碍(PTSD)的特定症状群有关。 侵入性再体验症状)。典型的RSN连通性和BOLD信号的区域幅度， 与创伤后应激障碍及其症状维度相关的基因构成了高度可遗传的表型(h2=0.4 -0.6)，这超过了基于任务的功能磁共振成像和大多数结构神经成像表型的遗传力。一个 暴露于创伤后发生创伤后应激障碍的遗传易感性长期以来一直被认为是假设的，现在 有证据支持。发现与脑沟通和脑连接有关的遗传因素 这些对创伤后应激障碍的贡献可能被证明对新的治疗突破至关重要。大脑连通性的耦合 关于它的遗传结构，绘制创伤后应激障碍的神经发生途径，以及关于神经和 遗传机制将支持精确医学指导的药物发现，用于管理精神疾病 跟随心理创伤。我们的目标是：1：研究功能基因结构的差异 与创伤后应激障碍相关的连接性疾病。2：探讨创伤后应激障碍在遗传性疾病中的作用 大脑结构和功能连接学的体系结构。3：调查创伤后应激障碍对联系的影响 基因转录结构和功能连接学之间的关系。大脑皮层功能的耦合 连接组学及其遗传结构和转录结构与已知干扰的关系 创伤后应激障碍的功能连接学可能为发现靶向治疗提供令人兴奋的机会。映射 创伤后应激障碍的神经发生通路与创伤后应激障碍症状的严重程度也将对未来的设计至关重要， 开发和选择尚未发现的治疗方法。了解它们独特的神经和基因 机制将对精确医学引导的药物发现至关重要，用于管理可能 跟随心理创伤。