Combining a novel framework for psychopathology with a precision medicine approach to understand the heterogeneous response to abstinence from alcohol

项目摘要 尽管以戒酒为导向的干预措施仍然是酒精使用障碍的典型治疗选择 (澳元)，复发是很常见的。对动物和人类的研究表明，在某些群体中，短期内 戒酒之后恢复饮酒会增加而不是减少随后的饮酒。这 反应的异质性可以在一定程度上解释AUD治疗效果不佳的原因，从而保证个性化治疗 何时开出以禁欲为导向的干预措施的规则。共同发生的精神病理学使澳州大学变得复杂， 使其成为临床决策的首要因素。该项目的总体目标是利用 一种新的精神病理学框架，精神病理学的层次分类(HiTOP)，以预测 对短期禁欲的不同反应，并检查共同的神经生物学和遗传学 这种反应背后的机制。这项申请的具体目的是1)刻画个人 谁受益于或受到基于HiTOP维度的短期强制禁欲的伤害 在控制良好的实验室范例中潜在的神经生物学和遗传机制2) 描述在自然饮酒期过后表现出酒精消费上升模式的个人 基于HiTOP维度以及潜在的神经生物学和遗传学的一年期间的戒酒 机械装置。将利用现代尖端子组发现方法，从而实现 同时模拟具有复杂、非线性的大量处理-调节剂相互作用 节制效应，以准确估计禁欲反应。这种尖端的方法直接 为临床决策提供信息，使创建预测戒酒反应的指南成为可能 练习一下。提议的项目具有创新性和重要意义，因为它1)研究了节欲的异质性 回应，这可能解释了酒精使用的升级，这是一个非常重要和代价高昂的问题；2)杠杆 用于个性化酒精治疗建议的新型HiTOP框架，易于评估 并可轻松应用于临床设置；3)采用尖端的现代统计方法， 解决精准医学中传统方法的局限性和个性化的迫切需要 治疗计划；4)补充数据驱动的方法，潜在的潜在神经生物学和 遗传机制；以及5)将新的、控制良好的人类实验室范例与生态学相结合 对真实世界报道的酒精模式进行有效的纵向跟踪，以进一步提供丰富和有力的发现。 这项研究的长期目标是制定指导方针，以促进临床医生的决定- 关于何时使用以禁欲为基础的干预。

Project Summary Although abstinence-oriented interventions remain the typical treatment choice for alcohol use disorder (AUD), relapse is common. Research in animals and humans shows that, in certain groups, short-term abstinence followed by reinstatement of drinking escalates, instead of reduces, subsequent alcohol use. This heterogeneity in response can in part explain poor AUD treatment effects, warranting personalized treatment rules for when to prescribe abstinence-oriented interventions. Co-occurring psychopathology complicates AUD, making it a prime factor on which to base clinical decision-making. The overall goal of this project is to utilize a novel psychopathology framework, the Hierarchical Taxonomy of Psychopathology (HiTOP), to predict the heterogeneous response to short-term abstinence and to examine shared neurobiological and genetic mechanisms underlying this response. The specific aims of this application are to 1) characterize individuals who benefit from, or are harmed by, short-term enforced abstinence based on HiTOP dimensions and underlying neurobiological and genetic mechanisms in a well-controlled laboratory paradigm and 2) Characterize individuals who show escalating patterns of alcohol consumption after natural periods of abstinence over a one-year period based on HiTOP dimensions and underlying neurobiological and genetic mechanisms. Modern cutting-edge subgroup discovery methodology will be leveraged which enables simultaneously modeling a large number of treatment-moderator interactions with complex, nonlinear moderation effects, to accurately estimate abstinence response. This cutting-edge methodology directly informs clinical decision making, enabling the creation of guidelines for predicting response to abstinence in practice. The proposed project is innovative and significant as it 1) studies heterogeneity in abstinence response, which might explain escalation in alcohol use, a highly significant and costly problem; 2) leverages the novel HiTOP framework for personalized alcohol treatment recommendations, which is easily assessed and can be easily applied to clinical settings; 3) applies cutting edge modern statistical methodology that addresses limitations of traditional methods in precision medicine and the urgent need for individualized treatment planning; 4) complements data-driven approaches with potential underlying neurobiological and genetic mechanisms; and 5) integrates a novel, well-controlled human laboratory paradigm with ecologically valid longitudinal follow-up of real-world reported alcohol patterns to further provide rich and robust findings. The long-term goal of this line of research is to develop guidelines to facilitate clinical practitioners’ decision- making concerning when to utilize abstinence-based interventions.