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

项目摘要/摘要 青少年酗酒(男性5+饮料，女性4+饮料)是有问题的，并与许多 消极的心理社会后果，如进展为早期和持续性酒精使用障碍(AUD)。 对青少年AUD的神经科学知情治疗的研究很少，但需要，而且必须量身定做 而不是从成人AUD文献中进行推断。这需要一个 全面了解青少年酗酒、酗酒对神经生物学的影响 饮酒青少年是青少年AUD药物治疗开发管道中的关键样本。 与不饮酒的同龄人相比，对酗酒青少年的神经生物学研究将有助于 确定酒精在发育中的大脑中的作用机制，这最终将转化为 青春期AUD的药物治疗进展。此外，酗酒对性别的神经影响 需要更好地了解，以确保对男性和女性都有效的治疗。建议进行的研究 采用多模式神经成像(磁共振波谱[MRS]和功能神经成像 [fMRI])研究神经代谢(用MRS测量)和神经行为(用fMRI测量) 与不饮酒对照相比，酗酒对青少年的影响。该项目将有助于解决 目前有关谷氨酸、氨基丁酸和谷胱甘肽(所有代谢物)神经代谢变化的文献缺口 酒精使用的失调)与青少年酗酒有关，以及这种变化与酒精的关系 提示反应性和性别作为生物变量(SABV)。目标1量化谷氨酸、GABA和谷胱甘肽 应用MRS Aim 2对酗酒者和不饮酒对照组的前扣带回皮质(ACC)进行比较 探索大脑代谢物水平(谷氨酸、GABA和谷胱甘肽)与酒精暗示之间的关系 与对照组相比，用fmri测量酗酒青年的反应性。AIM 3检查SABV在 与不饮酒对照相比，这些神经因素与青少年酗酒有关。调查结果将确定 青春期AUD药物治疗发展的神经靶点。此F32应用程序是 基于一项几乎完成的临床药物治疗试验(PI Squeglia)的基线神经成像数据， 增加一个未使用的控制组(Pi Kirkland；内部试点项目资金)，使其在 建议的时间表。此F32应用程序中提出的研究将作为基本的动手培训 促进应聘者在青少年酒精使用障碍、神经生物学和神经影像方面的职业发展 研究，它将产生一个数据集，在此数据集上使用高级 评估青少年AUD药物治疗前景的多模式成像平台。

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.