Department of Human Development and Family Studies, Purdue University, United States.
Department of Human Development and Family Studies, Purdue University, United States.
Neurosci Biobehav Rev. 2018 Sep;92:128-139. doi: 10.1016/j.neubiorev.2018.05.020. Epub 2018 May 23.
There are many theories about the mechanisms of associations between hypothalamic-pituitary-adrenal (HPA) function (indexed by cortisol) and substance use. However, the potential for genes that contribute to both HPA function and substance use to confound the association (e.g., genetic confounding) has largely been ignored. We explore the potential role of genetics in cortisol-substance use associations, build a conceptual framework placing theories and mechanisms for how cortisol and substance use are related into a developmental progression, and develop new hypotheses based on our findings. We conclude that the relationship between cortisol function and substance use is complex, occurs at multiple levels of analysis, and is bidirectional at multiple phases of the substance use progression. Additionally, there is potential for genetic confounding in cortisol-substance use associations, and thus a need for genetically informed designs to investigate how and why cortisol function is associated with substance use phenotypes from initiation through disorder. Gene-environment interplay and developmental context are likely to impact the effectiveness of prevention and intervention efforts to reduce substance use problems.
关于下丘脑-垂体-肾上腺 (HPA) 功能（以皮质醇为指标）与物质使用之间关联的机制有很多理论。然而，导致 HPA 功能和物质使用的基因可能会混淆这种关联（例如，遗传混淆），这在很大程度上被忽视了。我们探讨了遗传因素在皮质醇-物质使用关联中的作用，构建了一个概念框架，将皮质醇和物质使用之间关系的理论和机制置于一个发展过程中，并根据我们的发现提出了新的假设。我们得出结论，皮质醇功能与物质使用之间的关系是复杂的，发生在多个分析层面，并且在物质使用进展的多个阶段是双向的。此外，皮质醇-物质使用关联中存在遗传混淆的可能性，因此需要进行遗传信息设计，以研究皮质醇功能如何以及为何与物质使用表型相关，从开始到障碍。基因-环境相互作用和发展背景可能会影响预防和干预措施减少物质使用问题的效果。
