Neuroimaging of Children at Risk for Biopolar Disorder

描述（由申请人提供）：本项目的长期目标 指导以患者为导向的研究职业发展（K23）奖是为了 发展候选人在以病人为导向的临床研究中的技能，使他可以 成为儿童心理健康领域的独立研究者。博士 Chang的具体目标是熟练掌握儿科情绪障碍 研究，特别是在利用脑成像技术， 阐明与儿童临床表现相关的神经生物学数据 和青少年双相情感障碍（BD）。为了实现这一目标， 候选人将由神经影像学，儿童领域的专家指导 和成人BD，以及统计和研究设计。此外，候选人 将参加教育活动，在他的部门，以及正式的 在认知神经科学，脑成像领域的课程， 统计最后，候选人将密切开展研究项目 与他的研究训练计划一致拟议研究的目标 项目是收集纵向现象学和脑成像数据， 父母患有BD的儿童和青少年后代， 发展成躁郁症这些高危儿童，有些已经患有BD， 健康对照组将在三年内通过脑 功能性磁共振成像（fMRI）和质子磁共振成像 波谱（MRS）。fMRI任务将与情绪和注意力有关， 质子核磁共振将是双侧背外侧前额叶皮质（DLPFC）， 特别是评估N-乙酰天冬氨酸/肌酸酐（NAA/Cr）比率。 现象学将通过结构化诊断访谈进行评估， 临床医师评定量表和患者评定问卷。我们假设 (1)在基线时已经患有BD的风险后代将具有不同的区域， 激活和失活比健康对照，主要是在DLPFC和 前扣带皮层（ACC），（2）有BD风险的后代将有较低的 双侧DLPFC与健康对照组相比的NAA/Cr比值，以及（3）处于风险中 在本研究过程中发展BD的后代将表现出更大的 DLPFC NAA/Cr较基线降低，与对照组相比， 激活与基线或基线时已患有BD的受试者相似， 三年随访。通过开展这项研究项目， 研究培训计划的实施，张博士计划成为一名 儿科BD领域的独立研究者，因此有助于 目前对BD的神经生物学和发展的认识。

DESCRIPTION (provided by the applicant): The long-term objective of this Mentored Patient-Oriented Research Career Development (K23) Award is to develop the candidate's skills in patient-oriented clinical research so that he may become an independent researcher in the field of child mental health. Dr. Chang's specific goal is to gain proficiency in pediatric mood disorders research, specifically in the area of utilizing brain imaging techniques to elucidate neurobiological data correlated to clinical presentations of children and adolescents with bipolar disorder (BD). To accomplish this goal, the candidate will be mentored by experts in the field of neuroimaging, childhood and adult BD, and statistics and research design. The candidate furthermore will participate in educational activities in his department as well as formal coursework in the areas of cognitive neuroscience, brain imaging, and statistics. Finally, the candidate will carry out a research project closely aligned with his research training plan. The goal of the proposed research project is to gather longitudinal phenomenological and brain imaging data on child and adolescent offspring of parents with BD, who are at high risk for developing bipolar disorder. These at-risk children, some already with BD, and healthy controls will be assessed longitudinally over three years by brain functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS). fMRI tasks will be related to emotion and attention, and proton MRS will be of bilateral dorsolateral prefrontal cortices (DLPFC), specifically assessing n-acetyl aspartate/creatinine (NAA/Cr) ratios. Phenomenology will be assessed through structured diagnostic interviews, clinician-rated scales, and patient-rated questionnaires. We hypothesize that (1) at-risk offspring already with BD at baseline will have differing areas of activation and deactivation than healthy controls, primarily in DLPFC and anterior cingulate cortex (ACC), (2) at-risk offspring with BD will have lower NAA/Cr ratios in bilateral DLPFC compared to healthy controls, and (3) at-risk offspring who develop BD in the course of this study will demonstrate a greater decrease in DLPFC NAA/Cr from baseline than controls and patterns of brain activation similar to those subjects already with BD, either at baseline or at three-year follow-up. Through conducting this research project and implementation of the research training plan, Dr. Chang plans to become an independent investigator in the field of pediatric BD and thus contributing to the current knowledge of the neurobiology and development of BD.