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: 9913583
• 负责人: Danella Marie Hafeman
• 金额: $ 18.68万
• 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/9913583
• 关键词: 14 year old; Adolescent; Adult; Affective; Age; Amygdaloid structure; Area; Back; Bipolar Disorder; Brain; Brain region; Child; Childhood; Clinical; 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; Research; Research Activity; Research Personnel; Resources; Rest; Risk; Sampling; Scanning; Selection Criteria; Short-Term Memory; Signal Transduction; Testing; Time; 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; negative affect; neural circuit; neural correlate; neural network; neurodevelopment; neuroimaging; neuromechanism; novel; offspring; prevent; recruit; reduce symptoms; 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.

项目概要/摘要 患有双相情感障碍的父母的后代（“高危青少年”）患双相情感障碍的风险增加 精神病理学。这些高危青少年中的许多人情绪不稳定，情绪经常发生严重变化。 情绪状态，导致功能不良并增加情绪障碍的风险。然而，并非所有 有家族风险的个体会患上精神疾病，在这个项目中，我们探讨了补偿性的方法 网络可以帮助解释风险的个体差异。多项证据表明，神经 支持工作记忆（WM）的电路可能充当这样的补偿网络，并且更好地工作 记忆能力（WMC）尤其与更好的情绪调节和更少的情绪不稳定相关。这 该项目的目标是更好地了解情绪不稳定的神经回路，然后评估潜力 有双相情感障碍（BD）风险的青少年的补偿性神经机制。我们建议首先评估 高危青少年和健康青少年腹侧激活和功能连接 (FxC) 方面存在差异 参与情绪认知重评的网络，以及这些网络中的个体差异是否存在 与高危青少年的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 FxC） 中央执行网络（WM 的中心）可能会补偿这些腹侧异常，因此可能 与高危青少年的情绪不稳定程度较低有关。为了探究这种关系的方向性， 我们对一部分高危、不稳定的青少年进行了 WM 培训试点（5 周）。鉴定 这种针对高危青少年的补偿网络将为这些青少年提供预防措施的目标， 并为未来研究增强复原力的策略铺平道路。 与该研究计划相一致，培训目标将为首席研究员提供技能 有必要进一步开展这一研究：具体来说，发展认知神经科学的培训， 在儿科人群中实施神经影像学研究，并进行复杂的分析 神经影像数据。为了获得此培训，PI 组建了一支具有相关专业知识的指导团队 领域，最值得注意的是她的导师 Mary Phillips 博士（BD 神经影像学）和共同导师 Boris Birmaher 博士 （对患有 BD 的青少年进行研究）。她还设计了详细的训练计划，其中包括 与顾问、课程作业和研讨会的正式合作。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双相情感障碍研究的机构， 以及情感和认知神经科学，以及支持职业发展的良好记录 的初级教师。该培训将建立在 PI 作为儿童精神病学家的现有背景之上，具有很强的 统计学和临床​​神经科学知识，为她提供成为一名医生所需的技能 独立调查员。她的长期研究目标是更好地表征神经发育 青少年双相情感障碍的发展轨迹，并制定策略来增强那些面临疾病风险的人的复原力。