Miliano Cristina, Natividad Luis A, Quello Susan, Stoolmiller Mike, Gregus Ann M, Buczynski Matthew W, Mason Barbara J
School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas.
Biol Psychiatry Glob Open Sci. 2024 Jul 26;4(6):100368. doi: 10.1016/j.bpsgos.2024.100368. eCollection 2024 Nov.
Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by alcohol seeking and consumption despite negative consequences. Despite the availability of multiple treatments, patients continue to exhibit high relapse rates. Thus, biomarkers that can identify patients at risk for heightened craving are urgently needed. Mounting preclinical and clinical evidence implicates perturbations in bioactive lipid signaling in the neurobiology of craving in AUD. We hypothesize that these lipids are potential biomarkers for predicting alcohol craving in patients with AUD.
This study used archival deidentified clinical data and corresponding plasma specimens from 157 participants in 3 clinical studies of AUD. We evaluated plasma levels of 8 lipid species as predictors of craving in response to in vivo alcohol and affective cues during abstinence.
Participants were 109 men and 48 women who met DSM-5 criteria for severe AUD. We found that plasma levels of 12- and 15-HETE, 12/15-lipoxygenase-produced proinflammatory lipids, and palmitoylethanolamide, an anti-inflammatory fatty acid amide hydrolase-regulated lipid metabolite, were differentially correlated with alcohol craving during abstinence, predicting higher craving independent of demographics, alcohol use history, and multiple therapeutic treatments.
Our findings highlight the promise of these lipid metabolites as biomarkers of heightened alcohol craving. The results open a novel opportunity for further research and clinical evaluation of these biomarkers to optimize existing treatments and develop new therapeutics for AUD.
酒精使用障碍（AUD）是一种慢性复发性疾病，其特征是尽管存在负面后果仍寻求并饮用酒精。尽管有多种治疗方法，但患者的复发率仍然很高。因此，迫切需要能够识别有强烈渴望风险的患者的生物标志物。越来越多的临床前和临床证据表明，生物活性脂质信号的紊乱与AUD渴望的神经生物学有关。我们假设这些脂质是预测AUD患者酒精渴望的潜在生物标志物。
本研究使用了来自3项AUD临床研究的157名参与者的存档匿名临床数据和相应的血浆样本。我们评估了8种脂质的血浆水平，作为禁欲期间对体内酒精和情感线索产生渴望的预测指标。
参与者包括109名男性和48名女性，他们符合DSM-5中重度AUD的标准。我们发现，12-和15-HETE（12/15-脂氧合酶产生的促炎脂质）以及棕榈酰乙醇酰胺（一种抗炎脂肪酸酰胺水解酶调节的脂质代谢物）的血浆水平与禁欲期间的酒精渴望存在差异相关性，独立于人口统计学、饮酒史和多种治疗方法预测更高的渴望程度。
我们的研究结果突出了这些脂质代谢物作为酒精渴望增强生物标志物的前景。这些结果为进一步研究和临床评估这些生物标志物提供了新机会，以优化现有治疗方法并开发针对AUD的新疗法。
