Bardo M T, Charnigo R J, Shaykin J D, Malone S G, Ortinski P I, Turner J R
Department of Psychology, College of Arts and Sciences, University of Kentucky, USA.
Department of Biostatistics, College of Public Health, University of Kentucky, USA.
Neurosci Biobehav Rev. 2025 Jul;174:106175. doi: 10.1016/j.neubiorev.2025.106175. Epub 2025 Apr 23.
Among the various checklist items used to diagnose substance use disorders (SUDs), the most recent version of the Diagnostic and Statistical Manual (DSM-5) begins with three items that imply a loss of control characterized by taking increasingly larger amounts of the drug and for longer periods. This process, often called "escalation", has been modeled in laboratory animals with the goal of identifying the mechanisms associated with SUDs. The current review first summarizes the different interpretations used to explain escalation of drug intake. Next, we examine the various ways that escalation of intake has been defined in clinical populations and how preclinical models have captured this phenomenon in the laboratory. Next, we critically discuss the key issues relevant to statistical modeling of escalation of drug intake in both humans and non-human animals, with the goal of quantifying individual differences in escalation behavior that may be useful for identifying a SUD "phenotype". Although both preclinical and clinical data rarely consider individual differences in escalation as a discrete factor, we also summarize findings indicating that common models of escalated drug intake are associated with specific genetic and cellular changes. Building on this framework of investigation is intended to offer insights in understanding the trajectory of SUDs, thus uncovering novel avenues for prevention and treatment.
在用于诊断物质使用障碍（SUDs）的各种清单项目中，最新版的《精神疾病诊断与统计手册》（DSM - 5）开篇的三个项目暗示了一种失控状态，其特征是服用药物的量越来越大且时间越来越长。这个过程通常被称为“剂量递增”，已在实验动物身上进行模拟，目的是确定与物质使用障碍相关的机制。本综述首先总结了用于解释药物摄入量递增的不同解读。接下来，我们考察在临床人群中定义摄入量递增的各种方式，以及临床前模型在实验室中捕捉这一现象的方式。然后，我们批判性地讨论与人类和非人类动物药物摄入量递增的统计建模相关的关键问题，目标是量化摄入量递增行为中的个体差异，这可能有助于识别物质使用障碍的“表型”。尽管临床前和临床数据很少将摄入量递增中的个体差异视为一个离散因素，但我们也总结了相关研究结果，表明常见的药物摄入量递增模型与特定的基因和细胞变化有关。基于这一调查框架旨在为理解物质使用障碍的发展轨迹提供见解，从而揭示预防和治疗的新途径。
