Ventral Prefrontal Network Connectivity and Alcohol Sensitivity in Bipolar Disorder and Typically Developing Young Adults

双相情感障碍和典型发育中的年轻人的腹侧前额叶网络连接和酒精敏感性

• 批准号: 10315831
• 负责人: Dylan E Kirsch
• 金额: $ 2.04万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-01-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10315831
• 关键词: Acute; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; Amygdaloid structure; Anisotropy; Anti-Anxiety Agents; Award; Bipolar Disorder; Clinical; Cognitive deficits; Corpus striatum structure; Data; Development; Diffusion Magnetic Resonance Imaging; Early treatment; Educational process of instructing; Emotional; Exhibits; Fellowship; Fiber; Foundations; Functional Magnetic Resonance Imaging; Goals; Individual; Individual Differences; Intervention; Intoxication; Laboratories; Mental disorders; Mentors; Mentorship; Methodology; Modeling; Neurobiology; Nucleus Accumbens; Outcome; Participant; Placebo Control; Placebos; Prefrontal Cortex; Process; Reporting; Research; Research Training; Risk; Risk Factors; Role; Scientist; Structure; Testing; Training; Training Programs; Translating; Variant; Work; Writing; Youth; alcohol comorbidity; alcohol response; alcohol risk; alcohol sensitivity; alcohol use disorder; breath alcohol measurement; career; career development; design; disorder control; drinking behavior; endophenotype; experience; high risk; interest; neurobiological mechanism; neuroimaging; pre-doctoral; response; responsible research conduct; sedative; skill acquisition; statistics; stem; suicidal risk; treatment response; treatment strategy; white matter; young adult

PROJECT ABSTRACT This Ruth L. Kirschstein PreDoctoral Individual National Research Award describes a research and training program that will prepare the applicant, Dylan Kirsch, for a career as an independent research scientist focused on the role of psychiatric illness in alcohol use disorders. The proposed research plan will test neurobiological mechanisms that contribute to altered sensitivity to alcohol in bipolar disorder and typically developing young adults. Differences in subjective response to alcohol predict alcohol use problems and risk for alcohol use disorders in typically developing youth, however the mechanisms that contribute to this risk—or if similar mechanisms are observed—in psychiatric illness are unclear. We will test the hypothesis that structural connectivity within ventral prefrontal cortical networks is related to alcohol-induced changes in network functional connectivity, and therefore, subjective sensitivity to alcohol. Results from the project have the potential to inform our understanding of neurobiological mechanisms that contribute to risk for alcohol use disorders in bipolar disorder and typically developing young adults. The applicant and mentors, Drs. Elizabeth Lippard and Kim Fromme have designed a comprehensive research and training plan to test this hypothesis. The training plan emphasizes 1) conceptual training in the neurobiological mechanisms and clinical issues in bipolar and alcohol use disorders; 2) methodological training in advanced neuroimaging (functional connectivity and diffusion tensor imaging [DTI] methodology) and placebo-controlled alcohol administration; and 3) career development skills, including mentorship, statistics, teaching, writing, and responsible conduct of research. Research aims are to 1) determine if changes in ventral prefrontal network functional connectivity in response to alcohol—during emotional processing—are different in bipolar disorder, compared to typically developing young adults, and if alcohol-induced changes in functional connectivity within these networks relate to subjective response to alcohol; and 2) if structural connectivity within ventral prefrontal networks relates to subjective response to alcohol and alcohol-induced changes in functional connectivity. Young adults (ages 21-26) with bipolar disorder and typically developing controls (n=30 per group) will complete DTI at baseline and functional MRI during placebo-controlled laboratory alcohol administration sessions (within subject, counter-balanced). We predict alcohol will weaken functional connectivity in the ventral prefrontal network and that magnitude of change will be smaller in bipolar disorder, compared to controls, with smaller magnitude of change associated with lower subjective response to alcohol. We predict weaker structural connectivity will relate to lower subjective response to alcohol and smaller alcohol-induced changes in functional connectivity in both groups. Findings will aid in our understanding of the processes that contribute to differences in sensitivity to alcohol and suggest a neurobiological mechanism that contributes to sensitivity to alcohol and risk for alcohol use disorders. This fellowship is critical for the applicant to pursue her training objectives, test the hypothesis, and progress towards the next stage of her research career.

项目摘要 Ruth L. Kirschstein 博士前个人国家研究奖描述了一项研究和培训 该计划将为申请人迪伦·基尔希（Dylan Kirsch）做好准备，成为一名独立研究科学家，专注于 关于精神疾病在酒精使用障碍中的作用。拟议的研究计划将测试神经生物学 导致双相情感障碍和典型发育中的年轻人对酒精敏感性改变的机制 成年人。对酒精的主观反应的差异可预测饮酒问题和饮酒风险 典型发育中青少年的疾病，但是导致这种风险的机制——或者如果类似的话 观察到精神疾病的机制尚不清楚。我们将检验结构性假设 腹侧前额皮质网络内的连接性与酒精引起的网络功能变化有关 连接性，因此对酒精的主观敏感性。该项目的结果有可能提供信息 我们对导致双相情感障碍患者酒精使用障碍风险的神经生物学机制的理解 障碍和典型发育中的年轻人。申请人和导师，博士。伊丽莎白·利帕德和金 Fromme 设计了一个全面的研究和培训计划来检验这一假设。培训计划 强调 1) 双相情感障碍和酒精的神经生物学机制和临床问题的概念培训 使用障碍； 2）高级神经影像学方法培训（功能连接和扩散张量 成像 [DTI] 方法）和安慰剂控制的酒精给药； 3）职业发展技能， 包括指导、统计、教学、写作和负责任的研究行为。研究目标是 1) 确定腹侧前额叶网络功能连接的变化是否响应酒精——在 与典型发育中的年轻人相比，双相情感障碍的情绪处理是不同的，如果 酒精引起的这些网络内功能连接的变化与对酒精的主观反应有关； 2）腹侧前额叶网络内的结构连接是否与对酒精和酒精的主观反应有关 酒精引起的功能连接变化。患有双相情感障碍的年轻人（21-26 岁）通常 开发对照（每组 n = 30）将在安慰剂对照期间完成基线 DTI 和功能 MRI 实验室酒精管理课程（在主题内，平衡）。我们预测酒精会减弱 腹侧前额叶网络的功能连接，双相情感障碍的变化幅度会更小 与对照组相比，障碍的变化幅度较小，与较低的主观反应相关 酒精。我们预测较弱的结构连通性将与对酒精的主观反应较低和较小的 酒精引起两组功能连接的变化。研究结果将有助于我们理解 导致对酒精敏感性差异的过程，并提出了一种神经生物学机制 导致对酒精的敏感性和酒精使用障碍的风险。该奖学金对申请人至关重要 追求她的培训目标，检验假设，并迈向她研究生涯的下一阶段。