非依赖型问题饮酒者的外周免疫系统适应与饮酒动机
Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers.
作者信息
Milivojevic Verica, Ansell Emily, Simpson Christine, Siedlarz Kristen M, Sinha Rajita, Fox Helen C
机构信息
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Department of Psychology, Syracuse University, Syracuse, New York.
出版信息
Alcohol Clin Exp Res. 2017 Mar;41(3):585-595. doi: 10.1111/acer.13317. Epub 2017 Feb 1.
BACKGROUND
Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of this study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls.
METHODS
Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress [S], relaxing [R], and alcohol cue [C]), followed by the "alcohol taste test" (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, 1 per day in a randomized and counterbalanced order. Measures of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), alcohol craving, and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT.
RESULTS
Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress- and cue-induced alcohol craving and anxiety and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake, and severity of problem drinking.
CONCLUSIONS
Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.
背景
越来越多的证据表明，促炎细胞因子和抗炎细胞因子水平在酒精依赖中存在功能失调。此外，一些初步研究结果表明，外周炎症的这些适应性变化可能通过直接影响或应激反应性的间接影响，导致对酒精的渴望和问题饮酒。重要的是，促炎细胞因子和抗炎细胞因子在从健康饮酒发展到问题饮酒过程中的作用尚未完全明确。本研究的目的是评估与酒精相关的外周免疫系统变化是否会影响应激和酒精线索诱发的渴望、焦虑以及问题饮酒者在实验室中的行为性酒精动机和摄入量，并与社交饮酒的对照组进行比较。
方法
26名问题饮酒者和38名适度社交饮酒者参与了一项实验室挑战程序，在此过程中，他们暴露于3种个性化的5分钟意象条件下（应激[S]、放松[R]和酒精线索[C]），随后进行“酒精味觉测试”（ATT），作为隐性酒精动机和摄入量的衡量指标，连续3天进行，每天1次，采用随机和平衡顺序。在基线、意象暴露后立即以及在ATT中谨慎呈现啤酒线索时，评估肿瘤坏死因子-α（TNFα）、白细胞介素-6（IL-6）、白细胞介素-1受体拮抗剂（IL-1ra）、酒精渴望和焦虑水平。
结果
与适度饮酒者相比，问题饮酒者表现出IL-6和IL-1ra的持续性减弱。在问题饮酒者中，这些变化还伴随着应激和线索诱发的酒精渴望及焦虑水平的升高，并可预测激发的酒精渴望、行为性酒精动机和摄入量以及问题饮酒的严重程度。
结论
目前的研究结果表明，问题饮酒者的选择性免疫抑制可能在酒精摄入动机中起关键作用。
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