Frontotemporal Neural Systems in Biopolar Disorder and Schizophrenia

描述(由申请人提供)：这项职业发展指导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，包括多模式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)所涉及的额颞神经系统。应聘者在BD和SZ的研究中运用多模式神经成像技术和分子遗传学的丰富背景使她非常适合进行这项工作。利用上述技术，她建议在患有BD、SZ的个体和健康对照参与者之间进行直接比较，以阐明每种疾病涉及的不同病理生理学。BD和SZ中的新数据同时支持控制额颞叶神经系统发育的基因的重叠易感性，以及针对每个疾病的不同的额颞叶异常特征。BD的额颞神经系统异常集中在腹侧结构，包括腹侧前额叶和杏仁核；而SZ则涉及更多背侧区域，包括背侧、外侧前额叶皮质和海马区。此外，她还将研究神经调节蛋白1及其受体ErbB4的遗传变异对BD和SZ额颞神经系统的不同影响。培训部分将包括监督研究，正式课程，以及多模式神经成像技术和分子遗传学的高级培训。该项目在希拉里·布隆伯格、约翰·克里斯特尔、R·托德·康斯特布尔和乔尔·格勒恩特博士的指导下，与BD和SZ研究、神经成像分析、分子遗传学、神经成像研究的分子建模策略和临床神经科学的专家合作，进行了多学科的研究，将为候选人提供一个宝贵的机会来解决有关遗传变异对BD和SZ额颞神经系统的影响的问题。该项目将为候选人成为应用多模式神经成像和分子遗传学以确定BD和SZ潜在的额颞部神经系统异常的独立研究专家提供必要的重要支持和培训。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患者大脑异常分布的差异，并确定哪些基因可能对这种不同的分布起作用。这项工作将增强我们对这些障碍的原因的了解，增强我们及早发现这些障碍的能力，并开发新的更有效的治疗方法。最后，它将通过结合不同科学领域的先进研究技术，培训一名特别适合进行这项工作的调查员。

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.