Data_Sheet_1_Exploring the Relationship Between Substance Use and Allostatic Load in a Treatment/Research Cohort and in a US Probability Sample (NHANES 2009–2016).docx

Allostatic load, an operationalization for cumulative strain on physiology from adaptation (allostasis) to stress over a lifetime, can manifest as damage to cardiovascular, neuroendocrine, and metabolic systems. The concept of allostatic load may be particularly useful in research on substance-use disorders (SUDs) because SUD researchers have sought to better understand the relationship between chronic stressors and drug use. Theoretical models hold that SUDs can be conceptualized as a spiral toward a state of persistent allostasis (i.e., allostasis so persistent as to represent homeostasis at a new, unhealthy set point). Regardless of the extent to which those models are accurate, increased allostatic load could be a mechanism by which frequent drug administration increases risk for adverse outcomes. We conducted two secondary analyses to evaluate allostatic load in the context of drug use, including alcohol use, in a locally recruited sample with a high proportion of illicit substance use (N = 752) and in a nationally representative sample from the NHANES 2009–2016. We hypothesized that after controlling for age and other potential confounds, people with longer histories of drug use would have higher allostatic-load scores. Multiple regression was used to predict allostatic load from participants' drug-use histories while controlling for known confounds. In the locally recruited sample, we found that longer lifetime use of cocaine or opioids was related to increased allostatic load. In NHANES 2009–2016, we found few or no such associations. Lengthy histories of problematic non-medical substance use may facilitate more rapid increases in allostatic load than aging alone, and, together with findings from previous investigations, this finding suggests increased risk for chronic disease.

稳态负荷（allostatic load）是对个体一生中为适应压力而产生的生理累积负荷的操作化定义，可表现为心血管系统、神经内分泌系统与代谢系统的损伤。稳态负荷这一概念在物质使用障碍（SUDs）的相关研究中具有独特应用价值，因该领域研究者始终致力于深入解析慢性应激源与药物使用之间的关联。现有理论模型认为，物质使用障碍可被概念化为一种指向持续性稳态负荷的螺旋式进程——即此种稳态负荷持续存在，以至于在全新且不健康的平衡点上达成了稳态（homeostasis）。无论此类模型的准确性如何，稳态负荷升高都可能是频繁药物使用增加不良结局风险的潜在生物学机制。本研究开展两项二次分析，以评估药物使用（含酒精使用）场景下的稳态负荷水平，分析对象分为两类：一是本地招募的非法物质使用占比较高的样本（N=752），二是来自2009-2016年美国国家健康与营养检查调查（National Health and Nutrition Examination Survey, NHANES）的全国代表性样本。本研究提出如下假设：在控制年龄及其他潜在混淆变量后，药物使用史更长的个体，其稳态负荷得分会更高。研究采用多元回归分析，基于被试的药物使用史预测其稳态负荷得分，同时控制已知混淆变量的影响。在本地招募的样本中，研究发现终生使用可卡因或阿片类药物的时长与稳态负荷升高呈显著正相关；而在2009-2016年NHANES全国代表性样本中，未发现此类关联或仅存在极弱的关联。相较于单纯衰老，长期存在问题性非医疗物质使用史可能会加速稳态负荷的升高；结合既往研究结论，本研究发现提示此类人群的慢性病患病风险有所上升。