Frontotemporal Neural Systems in Biopolar Disorder and Schizophrenia

双相情感障碍和精神分裂症的额颞神经系统

• 批准号: 7712910
• 负责人: Fei Wang
• 金额: $ 17.9万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7712910
• 关键词: Address; Amygdaloid structure; Area; Bipolar Disorder; Brain; Clinical; Collaborations; Data; Development; Disease; Dorsal; Emotional; ErbB4 gene; Face; Genes; Genetic Variation; Goals; Hippocampus (Brain); Individual; Interdisciplinary Study; K-Series Research Career Programs; Lateral; Mentors; Mentorship; Molecular Genetics; Molecular Models; Nature; Neuregulin 1; Neurosciences; Participant; Predisposition; Prefrontal Cortex; Relative (related person); Research; Research Methodology; Research Personnel; Research Technics; Schizophrenia; Science; Stimulus; Structure; System; Techniques; Training; Training Support; Work; effective therapy; emotional stimulus; investigator training; molecular modeling; multidisciplinary; neuroimaging; novel; public health relevance; receptor; relating to nervous system; response

DESCRIPTION (provided by applicant): The goal of this Mentored Career Development Award proposal is to provide the candidate advanced training in integrating multidisciplinary research methods, including multimodal neuroimaging techniques and molecular genetics, to study the frontotemporal neural system involved in bipolar disorder (BD) and schizophrenia (SZ). The candidate's rich background implementing multimodal neuroimaging techniques and molecular genetics in the study of BD and SZ makes her uniquely suited to conduct this work. Utilizing the aforementioned techniques, she proposes to conduct direct comparisons between individuals with BD, SZ and healthy comparison participants necessary to elucidate the distinct pathophyisology involved in each disorder. Emerging data in BD and SZ simultaneously support overlapping susceptibility to genes that regulate the development of frontotemporal neural systems as well as features offrontotemporalabnormalities that are distinct to each disorder. Frontotemporal neural system abnormalities in BD are centered in more ventral structures including ventral prefrontal cortex and amygdala; while deficits in more dorsal areas are implicated in SZ including dorsal lateral prefrontal cortex and the hippocampus. Furthermore, she will investigate the differential impact of genetic variation in neuregulin 1 and its receptor ErbB4 on the frontotemporal neural systems in BD and SZ. Training components will include supervised research, formal coursework, and advanced training in multimodal neuroimaging techniques and molecular genetics. The multidisciplinary nature of this project, conducted under the mentorship of Drs. Hilary Blumberg, John Krystal, R. Todd Constable and Joel Gelernter, in collaboration with experts in BD and SZ research, neuroimaging analysis, molecular genetics, molecular modeling strategies for neuroimaging studies and clinical neuroscience will provide a valuable opportunity for the candidate to address issues regarding the effects of genetic variation on the frontotemporal neural systems in BD and SZ. The project will provide the vital support and training necessary for the candidate to become an independent investigator expert in the application of multimodal neuroimaging and molecular genetics to identify underlying frontotemporal neural system abnormalities in BD and SZ. PUBLIC HEALTH RELEVANCE: This project aims to investigate differences in the distribution of brain abnormalities in bipolar disorder and schizophrenia and to determine which genes may contribute to the distinct distributions. This work will enhance our understanding of the causes of these disorders, our ability to detect the disorders early and to develop novel and more effective treatments. Finally, it will enable the training of an investigator uniquely suited to conduct this work by combining advanced research techniques from various fields of science.

描述（由申请人提供）：本导师职业发展奖提案的目标是为候选人提供综合多学科研究方法的高级培训，包括多模态神经成像技术和分子遗传学，以研究双相情感障碍（BD）和精神分裂症（SZ）的额颞叶神经系统。候选人在BD和SZ研究中应用多模态神经成像技术和分子遗传学的丰富背景使她非常适合开展这项工作。利用上述技术，她建议在BD、SZ个体和健康对照参与者之间进行直接比较，以阐明每种疾病所涉及的独特病理生理学。BD和SZ的新数据同时支持对调节额颞叶神经系统发育的基因的重叠易感性，以及每种疾病不同的额颞叶异常特征。双相障碍的额颞神经系统异常多集中在腹侧结构，包括腹侧前额叶皮层和杏仁核；而更多背侧区域的缺陷与SZ有关，包括背侧前额叶皮层和海马。此外，她将研究神经调节蛋白1及其受体ErbB4的遗传变异对BD和SZ额颞叶神经系统的差异影响。培训内容将包括监督研究、正式课程和多模态神经成像技术和分子遗传学的高级培训。该项目的多学科性质，在博士的指导下进行。Hilary Blumberg、John Krystal、R. Todd Constable和Joel Gelernter将与BD和SZ研究、神经成像分析、分子遗传学、神经成像研究和临床神经科学的分子建模策略方面的专家合作，为候选人提供一个宝贵的机会，解决遗传变异对BD和SZ额颞叶神经系统的影响问题。该项目将为候选人提供重要的支持和必要的培训，使其成为应用多模式神经成像和分子遗传学来识别BD和SZ潜在的额颞叶神经系统异常的独立研究者专家。公共卫生相关性：该项目旨在调查双相情感障碍和精神分裂症中大脑异常分布的差异，并确定哪些基因可能导致这种不同的分布。这项工作将提高我们对这些疾病的病因的理解，提高我们早期发现这些疾病的能力，并开发出新的更有效的治疗方法。最后，它将通过结合来自各个科学领域的先进研究技术，使培养一名独特适合开展这项工作的研究者成为可能。