Neurodevelopmental Origins of Emotion Dysregulation in Borderline Personality

描述（由申请人提供）：本导师研究科学家发展奖的目的是促进候选人发展成为一名成功的临床神经科学研究人员，研究边缘型人格障碍（BPD）的神经发育基础，特别是青少年认知和情绪控制过程成熟的作用。情绪失调和冲动是BPD的典型特征，通常出现在青春期，并与BPD相关损害的持久性有关。拟议的K01奖的直接研究重点是验证以下假设：青春期这些BPD症状的发展反映了青春期纹状体、边缘和前额叶大脑区域之间的连接成熟功能失调，这些区域分别支持接近、回避和调节神经行为系统。该候选人在研究BPD的发展精神病理学相关的几个领域具有专长，包括1)使用实验室范式评估认知和情绪控制过程，2)控制过程与情绪失调之间的行为和心理生理联系，以及3)使用纵向数据分析方法表征BPD的发展轨迹。在此专业知识的基础上，特别关注BPD的神经基础，候选人将获得以下方面的进一步培训：1)研究自我调节过程的发育神经科学方法，2)BPD的发育精神病理学，以及3)功能和有效的连接分析，以阐明青春期区域间连接的发展变化。拟议的研究和培训活动将由Beatriz Luna博士（本奖项的主要导师）指导的神经认知发展实验室提供支持，Beatriz Luna博士是一位著名的发育神经科学家，其研究主要集中在青春期奖励和控制过程的长期成熟上。在获奖期间，候选人将在健康对照和BPD症状个体中进行fMRI研究，以表征青春期和成年早期亚一般前扣带皮层、腹侧纹状体和杏仁核之间区域间连接的成熟。利用功能和有效连通性分析，本研究将表征情绪冲突任务中边缘-前额叶和纹状体-前额叶影响的平衡。该研究还将在18个月的随访期内探索额纹状体边缘连通性与BPD症状发展轨迹之间的潜在关系。与国家心理健康研究所的优先事项一致，拟议的奖励有可能利用新的神经生物学方法确定BPD发展中的关键风险窗口。此外，拟议的奖励将提供培训和研究经验，这将推动候选人进入一个成功的研究生涯，研究BPD的神经发育。

DESCRIPTION (provided by applicant): The aim of this Mentored Research Scientist Development Award is to facilitate the candidate's development into a successful clinical neuroscience researcher investigating the neurodevelopmental basis of borderline personality disorder (BPD), particularly the role of adolescent maturation of cognitive and emotional control processes. Emotion dysregulation and impulsivity are prototypic features of BPD that typically emerge during adolescence and are associated with the persistence of BPD-related impairment over time. The immediate research priority of the proposed K01 award is to test the hypothesis that the development of these BPD symptoms in adolescence reflects dysfunctional adolescent maturation of connections among striatal, limbic, and prefrontal brain regions that support approach, avoidance, and modulatory neurobehavioral systems, respectively. The candidate has expertise in several domains relevant to studying the developmental psychopathology of BPD, including 1) the assessment of cognitive and emotion control processes using laboratory paradigms, 2) the behavioral and psychophysiological links between control processes and emotion dysregulation, and 3) the use of longitudinal data analytic methods to characterize developmental trajectories in BPD. To build upon this expertise and to focus specifically on the neural basis of BPD, the candidate will obtain further training in 1) developmental neuroscience approaches to the study of self-regulatory processes, 2) developmental psychopathology of BPD, and 3) functional and effective connectivity analyses to elucidate developmental changes in interregional connectivity during adolescence. Proposed research and training activities will be supported by the Laboratory of Neurocognitive Development directed by Dr. Beatriz Luna (primary mentor for this award), a noted developmental neuroscientist whose research has focused primarily on the protracted maturation of reward and control processes during adolescence. During the award, the candidate will conduct an fMRI study to characterize the maturation of interregional connectivity among the subgenual anterior cingulate cortex, ventral striatum, and amygdala during adolescence and early adulthood in healthy controls and individuals with BPD symptoms. Using functional and effective connectivity analyses, this study will characterize the balance of limbic-prefrontal and striatal- prefrontal influence during an emotion conflict task. The proposed research will also explore the prospective relationship between fronto-striatal-limbic connectivity and the developmental trajectory of BPD symptoms over an 18-month follow-up period. Consistent with the priorities of the National Institute of Mental Health, the proposed award has the potential to identify critical risk windows in the development of BPD using novel neurobiological methods. Further, the proposed award will provide the training and research experiences that will propel the candidate into a successful research career studying the neurodevelopment of BPD.