Emotion Regulation in Children of Parents with Bipolar Disorder

描述（由申请人提供）：本NIMH指导的以患者为导向的研究职业发展（K-23）奖申请的目的是支持我的长期职业目标，即整合创新的神经成像技术和情绪调节机制，以了解双相情感障碍（BD）的神经发育。我以前的培训是在现象学和磁共振成像（MRI）形态学分析的儿童在家庭风险发展BD。以往双相情感障碍后代神经影像学研究的一个局限性是对这一脆弱群体情绪调节的潜在潜在机制评估不足，不依赖于与疾病发作相关的混淆，如同时发生的精神疾病、药物暴露和物质使用。因此，为了实现我的职业目标，最大限度地将体内神经成像技术应用于高危临床人群，我建议通过参与课程工作，教学阅读，指导，和经验学习活动，补充拟议的研究活动。BD是一种普遍的、终身的、进行性的疾病，通常在青春期或成年早期开始。BD的主要症状是情绪失调。大脑和小脑区域，包括前额叶皮层，腹侧纹状体，杏仁核，海马和小脑蚓部已被证明可以调节患有BD的儿童和青少年以及具有BD家族风险的儿童和青少年的情绪过程。我的短期目标是应用功能磁共振成像和磁共振波谱，结合情感神经科学中使用的奖励和信息处理范式，阐明有家族性BD风险的青春期前儿童情绪调节的功能和神经化学基础。在这个项目中获得的数据将为未来的纵向研究提供信息，以促进我们对这种疾病发展中涉及的风险和保护因素的理解。拟议的综合研究和培训计划，加上斯坦福大学强大的研究环境，将促进我的发展成为一个独立的研究领域的BD的神经发育。公共卫生相关性：尽管在儿童双相情感障碍（BD）的识别方面取得了重大进展，但在过去十年中，治疗反应和结局的关键指标保持不变或恶化。鉴于青年BD临床诊断率的增加，很明显，需要新的概念方法来实现这些人群的有利长期结局。拟议的研究将有助于确定可改变的BD风险因素，从而防止儿童及其家庭的不良后果。

DESCRIPTION (provided by applicant): The purpose of this NIMH Mentored Patient-Oriented Research Career Development (K-23) Award application is to support my long-term career objective of integrating innovative neuroimaging techniques and mechanisms of emotion regulation to understand the neurodevelopment of Bipolar Disorder (BD). My previous training is in the phenomenology and Magnetic Resonance Imaging (MRI) morphometric analyses of children at familial risk for developing BD. One limitation of previous neuroimaging studies in bipolar offspring is the inadequate assessment of the potential underlying mechanisms of emotion regulation in this vulnerable cohort, independent of confounds associated with illness onset, such as co-occurring psychiatric conditions, medication exposure, and substance use. Therefore, to achieve my career goal of maximizing the application of in vivo neuroimaging techniques to at-risk clinical populations, I propose to gain expertise integrating pediatric investigations of emotion regulation and dysregulation, functional (fMRI), magnetic resonance spectroscopy (MRS), statistical analyses, and the ethical conduct of research by participating in course work, didactic readings, mentoring, and experiential learning activities that complement the proposed research activities. BD is a prevalent, life-long, progressive disease that typically begins in adolescence or early adulthood. A cardinal symptom of BD is emotion dysregulation. Brain and cerebellar regions, including the prefrontal cortex, ventral striatum, amygdala, hippocampus, and cerebellar vermis have been shown to modulate emotional processes in children and adolescents with, and at familial risk for, BD. My short-term goal is to apply fMRI and MRS, in conjunction with reward and information-processing paradigms used in affective neuroscience, to elucidate the functional and neurochemical bases for emotion regulation in preadolescent children at familial risk for developing BD. Data obtained in this project will inform future longitudinal studies to facilitate the advancement of our understanding of risk and protective factors that are involved in the development of this illness. The proposed integrated research and training programs, together with the strong research environment of Stanford University, will foster my development into an independent investigator in the field of the neurodevelopment of BD. PUBLIC HEALTH RELEVANCE: Despite major improvements in the identification of pediatric bipolar disorder (BD), key indicators of treatment response and outcome have remained unchanged or worsened over the past decade. Given increasing rates of clinical diagnosis of BD in youth, it is clear that new conceptual approaches are required to achieve gains in favorable long-term outcomes in these populations. The proposed research will help to identify modifiable risk factors for BD that could prevent adverse outcomes for children and their families.