Utilizing multimodal neuroimaging to identify neurometabolic and neurobehavioral correlates of adolescent binge drinking

利用多模式神经影像学来识别青少年酗酒的神经代谢和神经行为相关性

• 批准号: 10535598
• 负责人: Anna E Kirkland
• 金额: $ 6.99万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2025-08-07
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10535598
• 关键词: 21 year old; Address; Adolescence; Adolescent; Adolescent Development; Adult; Alcohol abuse; Alcohol consumption; Alcohols; Anterior; Applications Grants; Biological; Brain; Centers of Research Excellence; Clinical; Clinical Research; Clinical Trials; Control Groups; Data; Data Analyses; Data Set; Development; Early Intervention; Ensure; Female; Female Adolescents; Functional Magnetic Resonance Imaging; Funding; Future; Glutamates; Glutathione; Goals; Healthcare Systems; Human; Imaging Techniques; Individual; K-Series Research Career Programs; Knowledge; Literature; Magnetic Resonance Spectroscopy; Male Adolescents; Measures; Meta-Analysis; Multimodal Imaging; Neurobiology; Neurocognitive; Neurosciences; Outcome; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Population; Publishing; Research; Sampling; Secure; Sex Differences; Societies; Specialized Center; Techniques; TimeLine; Training; Translating; United States National Institutes of Health; Youth; adolescent alcohol treatment; adolescent binge drinking; aged; alcohol cue; alcohol effect; alcohol use disorder; binge drinker; binge drinking; career development; cingulate cortex; cost; cue reactivity; efficacious treatment; emerging adult; experience; gamma-Aminobutyric Acid; hands on research; imaging platform; male; multimodal neuroimaging; multimodality; neural correlate; neurobehavioral; neurochemistry; neurodevelopment; neuroimaging; neuromechanism; peer; psychosocial; relating to nervous system; sex; therapy development; underage drinking; young adult

PROJECT SUMMARY/ABSTRACT Adolescent binge drinking (5+ drinks for males, 4+ drinks for females) is problematic and associated with many negative psychosocial consequences, such as progression into early and persistent alcohol use disorder (AUD). Research on neuroscience-informed treatments for adolescent AUD is sparse, but needed, and must be tailored to the adolescent population rather than extrapolating from the adult AUD literature. This requires a comprehensive knowledge of the neurobiological effects of problematic alcohol use in youth, making binge drinking adolescents a critical sample in the adolescent AUD pharmacotherapy development pipeline. Neurobiological research within binge drinking adolescents, as compared to their non-drinking peers, will help to identify mechanisms of alcohol action in the developing brain, which will ultimately translate to targets for pharmacotherapy development for adolescent AUD. Additionally, sex-specific neural effects of binge drinking need to be better understood to ensure efficacious treatments for both males and females. The proposed study employs multimodal neuroimaging (magnetic resonance spectroscopy [MRS] and functional neuroimaging [fMRI]) to investigate the neurometabolic (measured with MRS) and neurobehavioral (measured with fMRI) effects of binge drinking in youth, as compared to non-drinking controls. This project will help to address the current literature gap concerning neurometabolic alterations in glutamate, GABA, and glutathione (all metabolites dysregulated by alcohol use) associated with adolescent binge drinking, and how such changes relate to alcohol cue reactivity and sex as a biological variable (SABV). Aim 1 quantifies glutamate, GABA, and glutathione in the anterior cingulate cortex (ACC) in binge drinkers, as compared to non-drinking controls, using MRS. Aim 2 explores the association between brain metabolite levels (glutamate, GABA, and glutathione) and alcohol cue reactivity measured with fMRI in binge drinking youth, as compared to controls. Aim 3 examines SABV within these neural correlates of adolescent binge drinking, as compared to non-drinking controls. Findings will identify neural targets for the development of pharmacotherapy treatments for adolescent AUD. This F32 application is built upon baseline neuroimaging data from a nearly complete clinical pharmacotherapy trial (PI Squeglia) with an added non-using control group (PI Kirkland; internal pilot project funding), making it highly feasible within the proposed timeline. The research proposed in this F32 application will serve as essential hands-on training to promote the candidate’s career development in adolescent alcohol use disorder neurobiology and neuroimaging research, and it will result in a dataset on which to build an NIH K-award grant application using an advanced multimodal imaging platform to evaluate promising pharmacotherapies for adolescent AUD.

项目摘要/摘要 青少年饮酒（男性5杯以上，女性4多种饮料）是有问题的，并且与许多 负面的社会心理后果，例如发展为早期和持续性饮酒障碍（AUD）。 关于青少年AUD的神经科学知识治疗的研究很少，但需要量身定制 到青少年人口，而不是从成人声学文献中推断出来。这需要一个 对有问题的饮酒对青年的神经生物学影响的全面了解，使暴饮暴食 饮酒青少年是青少年AUD药物疗法开发管道中的关键样本。 与非饮酒的同龄人相比，暴饮暴食青少年内的神经生物学研究将有助于 确定发育中大脑中酒精作用的机制，最终将转化为目标 青少年AUD的药物疗法开发。此外，暴饮暴食的性别特异性神经效应 需要更好地理解以确保男性和女性的有效治疗。拟议的研究 员工多模式神经成像（磁共振光谱[MRS]和功能性神经影像学 [fMRI]）研究神经代谢（用MRS测量）和神经行为（用fMRI测量） 与非饮用的对照相比，青年饮酒的影响。该项目将有助于解决 有关谷氨酸，GABA和谷胱甘肽的神经代谢改变的当前文献差距（所有代谢物 与青少年饮酒相关的酒精饮酒失调以及这种变化与酒精有关 提示反应性和性别作为生物变量（SABV）。 AIM 1量化谷氨酸，GABA和谷胱甘肽 与非饮用的对照相比，使用MRS相比，暴饮暴食者的前扣带回皮质（ACC）。目标2 探索脑代谢物水平（谷氨酸，GABA和谷胱甘肽）与酒精提示之间的关联 与对照组相比，在暴饮暴食青年中用fMRI测量的反应性。 AIM 3考试SABV 与非饮食对照相比，这些青少年饮酒的神经自我反相。调查结果将确定 为青少年AUD开发药物治疗的神经靶标。此F32应用程序是 基于一项几乎完整的临床药物治疗试验（PI Squeglia）的基线神经成像数据 一个不利用的对照组（Pi Kirkland；内部飞行员项目资金），使其非常可行 建议的时间表。该F32申请中提出的研究将作为基本的动手培训 促进候选人在青少年酒精使用障碍神经生物学和神经影像学方面的职业发展 研究，这将导致一个数据集，可以在该数据集上使用高级 多模式成像平台评估青少年aud的承诺药物疗法。