Compensatory Neural Networks for the Cognitive Control of Emotion in Youth at Risk for Bipolar Disorder

用于双相情感障碍青少年情绪认知控制的补偿神经网络

• 批准号: 9309455
• 负责人: Danella Marie Hafeman
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-18 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309455
• 关键词: 14 year old; Adolescent; Adult; Affective; Age; Amygdaloid structure; Area; Back; Biological Neural Networks; Bipolar Disorder; Brain; Brain region; Child; Childhood; Clinical; Cognitive; Collaborations; Data; Development; Diagnosis; Early Intervention; Educational workshop; Emotions; Faculty; Family; Financial compensation; Future; Goals; Individual; Individual Differences; Institution; Instruction; Intervention; Knowledge; Lateral; Lead; Longitudinal Studies; Mediating; Mental Depression; Mental disorders; Mentors; Mentorship; Meta-Analysis; Methods; Mood Disorders; Moods; Neurosciences; Onset of illness; Outcome; Parents; Pattern; Phenotype; Population; Prefrontal Cortex; Preventive; Preventive measure; Principal Investigator; Psychiatrist; Psychopathology; Recruitment Activity; Research; Research Activity; Research Personnel; Resources; Rest; Risk; Sampling; Scanning; Selection Criteria; Short-Term Memory; Signal Transduction; Testing; Training; Training Activity; Training Programs; Universities; Vulnerable Populations; Work; Youth; affective neuroscience; base; behavior measurement; career development; childhood bipolar disorder; cognitive ability; cognitive control; cognitive neuroscience; cognitive reappraisal; design; disorder risk; early adolescence; emotion dysregulation; emotion regulation; emotional stimulus; habituation; improved; neural circuit; neural correlate; neurodevelopment; neuroimaging; neuromechanism; novel; offspring; prevent; relating to nervous system; resilience; response; skills; statistics; success

PROJECT SUMMARY / ABSTRACT Offspring of parents with bipolar disorder (“at-risk youth”) are at increased risk for the development of psychopathology. Many of these at-risk youth have elevated mood lability, frequent and severe changes in mood state, which contributes to poor functioning and increases risk for mood disorder. However, not all individuals at familial risk develop psychiatric disorders, and in this project we explore the compensatory networks that could help to explain individual differences in risk. Several lines of evidence indicate that neural circuitry supporting working memory (WM) might act as such a compensatory network, and that better working memory capacity (WMC) in particular is associated with better emotion regulation and less mood lability. The objective of this project is to better understand the neural circuitry of mood lability, and to then assess potential compensatory neural mechanisms in youth at risk for bipolar disorder (BD). We propose to first assess differences between at-risk and healthy youth in the activation and functional connectivity (FxC) of ventral networks involved in cognitive reappraisal of emotion, and whether the individual differences in these networks correlate with degree of mood lability in the at-risk youth. We next evaluate if a greater WMC (and FxC of the central executive network, central to WM) might compensate for these ventral abnormalities, and thus might be associated with less mood lability in at-risk youth. To provide a probe of the directionality of this relationship, we conduct a pilot manipulation of WM training (5 weeks) in a subset of at-risk, labile youth. Identification of such a compensatory network in at-risk youth would provide a target for preventive measures in these youth, and pave the way for future studies investigating strategies for building resilience. In concert with this research plan, training goals will provide the Principal Investigator with a skillset necessary to further pursue this line of research: specifically, training in developmental cognitive neuroscience, the implementation of neuroimaging studies in pediatric populations, and sophisticated analysis of neuroimaging data. To obtain this training, the PI has assembled a mentorship team with expertise in relevant areas, most notably, her mentor Dr. Mary Phillips (neuroimaging in BD) and co-mentor Dr. Boris Birmaher (implementation of studies of youth with BD). She has also designed a detailed training plan, which includes formal collaborations with consultants, coursework, and workshops. Research and training activities will primarily occur at the University of Pittsburgh, an institution with a commitment to research in pediatric BD, as well as affective and cognitive neuroscience, and a strong track record for supporting the career development of junior faculty. This training will build on the PI’s existing background as a child psychiatrist with a strong knowledge of statistics and clinical neuroscience, to provide her will the necessary skills to become an independent investigator. Her long-term research goal is to better characterize the neurodevelopmental trajectory of BD in youth, and develop strategies for building resilience in those who are at risk for disorder.

项目摘要/摘要 父母患有双相情感障碍的子女(“高危青少年”)患抑郁症的风险增加 精神变态学。这些高危青年中的许多人情绪不稳定，经常和严重的变化 情绪状态，这会导致功能不佳，增加情绪障碍的风险。然而，并不是所有的 处于家庭风险中的个体会发展成精神障碍，在这个项目中，我们将探索补偿性的 可以帮助解释风险个体差异的网络。多条证据表明，神经细胞 支持工作记忆(WM)的电路可以起到这样的补偿网络的作用，更好地工作 特别是记忆能力(WMC)与更好的情绪调节和更少的情绪不稳定有关。这个 这个项目的目标是更好地理解情绪不稳定的神经回路，然后评估潜力 双相情感障碍(BD)高危青年的代偿神经机制。我们建议首先评估 高危青年与健康青年腹侧核激活及功能连接性的差异 网络涉及对情绪的认知再评价，以及这些网络中的个体差异是否 高危青少年情绪不稳定程度与情绪不稳定程度相关。接下来，我们评估是否有更大的WMC(以及 中枢执行网络)可能补偿这些腹侧异常，因此可能是 与高危青年的情绪不稳定有关。为了提供对这种关系的方向性的探索， 我们在一组高危、不稳定的年轻人中进行了WM训练的试点操作(5周)。身份识别 这种边缘青年补偿性网络将为这些青年的预防措施提供一个目标， 并为未来研究建立复原力的策略铺平道路。 与这项研究计划相一致，培训目标将为首席调查员提供技能 进一步开展这一研究的必要性：具体地说，发展认知神经科学方面的培训， 在儿科人群中实施神经成像研究，并对 神经成像数据。为获得这项培训，公安部组建了一支具有相关专业知识的辅导小组。 最值得注意的是，她的导师玛丽·菲利普斯博士(BD神经成像)和共同导师鲍里斯·伯马赫博士 (开展对患有BD的青少年的研究)。她还设计了详细的培训计划，其中包括 与顾问、课程作业和研讨会的正式协作。研究和培训活动将 主要发生在匹兹堡大学，这是一家致力于儿科BD研究的机构，因为 以及情感和认知神经科学，以及在支持职业发展方面的良好记录 初级教职员工。这项培训将建立在私家侦探作为儿童精神病学家的现有背景基础上， 统计学和临床神经科学知识，为她的意志提供必要的技能，成为 独立调查员。她的长期研究目标是更好地描述神经发育 在青少年中建立BD的轨迹，并制定战略，以培养那些有障碍风险的人的复原力。