Neuroscience Studies on Early Detection of Schizophrenia

描述（由申请人提供）：这是一个NIMH指导的以患者为导向的研究职业发展奖（K23）的申请。候选人的兴趣是精神分裂症的早期识别和治疗。他曾在精神分裂症的现象学和早期临床过程中进行研究。这个职业发展计划将使他能够追求1）精神分裂症早期检测方法的专业培训，以及2）进行基因型-表型关联分析所需程序的培训。培训将包括由爱荷华州大学精神分裂症研究和分子遗传学专家进行个人指导，以及在领导精神分裂症预防研究的外部顾问的实验室进行培训。该培训计划还将与一项研究计划密切结合，该计划侧重于调查两个候选基因（脑源性神经营养因子（BDNF）和分裂症1（DISC 1））及其与精神分裂症两种定量表型（神经认知功能障碍和MRI脑容量不足）的关系。该研究计划的目的是1）确定BDNF和DISC 1的神经认知和MRI脑形态学相关性，2）研究精神分裂症先证者未受影响的兄弟姐妹的神经认知功能障碍和结构性脑缺陷。这个综合职业发展计划提供高风险研究方法，分子遗传学，认知神经科学和生物统计学方面的培训，将提高候选人将生物（例如内表型特征，遗传变异）和临床（例如前驱症状，家族史）风险因素结合到多阶段筛查计划中的能力，以早期识别精神分裂症。总之，培训计划和研究计划为科学发现提供了潜力，并为建立独立的研究生涯提供了支持。

DESCRIPTION (provided by applicant): This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K23). The candidate's interest is in the early identification and treatment of schizophrenia. He has previously conducted research in the phenomenology and early clinical course of schizophrenia. This career development program will allow him to pursue 1) specialized training in the methods of early detection in schizophrenia, and 2) training in the procedures necessary to conduct genotype-phenotype association analyses. Training will include individual mentoring by experts in schizophrenia research and molecular genetics at the University of Iowa, as well as training at the laboratories of external consultants who are leading the research in schizophrenia prevention. The training program will also be closely integrated with a research plan focusing on the investigation of two candidate genes (brain-derived neurotrophic factor (BDNF) and Disrupted-in-Schizophrenia 1 (DISC1)) and their relationships with two quantitative phenotypes of schizophrenia (neurocognitive dysfunction and MRI brain volume deficits). The aims of the research plan are 1) to identify neurocognitive and MRI brain morphometric correlates of BDNF and DISC1, and 2) to study neurocognitive dysfunction and structural brain deficits in unaffected siblings of schizophrenia probands. This integrated career development program, providing training in high-risk research methodology, molecular genetics, cognitive neuroscience and biostatistics, will enhance the candidate's ability to combine biological (e.g. endophenotypic traits, genetic variations) and clinical (e.g. prodromal symptoms, familial history) risk factors into multi-stage screening programs for the early identification of schizophrenia. Taken together, the training program and research plan provide the potential for scientific discovery as well as support for the establishment of an independent research career.