Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Alcohol Clin Exp Res. 2021 May;45(5):922-933. doi: 10.1111/acer.14588. Epub 2021 Apr 16.
Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD.
Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo-continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel-wise CBF comparisons were set at threshold of p < 0.05 cluster-corrected for multiple comparisons, voxel-level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions.
Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate-induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions.
This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence.
酒精使用障碍（AUD）与大脑生理过程的调节异常有关。乙酸盐是乙醇的代谢物，已被牵涉到几种在 AUD 中被破坏的过程中，包括转录调控、代谢、炎症和神经传递。为了进一步了解乙酸盐对 AUD 患者大脑功能的影响，我们研究了乙酸盐对大脑血流（CBF）、全身炎症细胞因子和 AUD 行为的影响。
从一个非医疗、临床管理的戒毒中心招募了 16 名 AUD 参与者。每个参与者按随机顺序接受乙酸盐和安慰剂输注，并接受 3T MR 扫描，使用定量假性连续动脉自旋标记。参与者和研究团队对输注情况不知情。使用混合效应线性回归模型，考虑到输注顺序，从丘脑提取的 CBF 值（ml/100 g/min）在安慰剂和乙酸盐之间进行比较。在设定的 p < 0.05 簇校正的多重比较的阈值下，进行体素水平的 CBF 比较，体素水平 p < 0.0001。还在输注之间评估了血浆细胞因子水平和行为。
共有 15 名男性和 1 名女性被纳入研究，他们的酒精使用障碍识别测试（AUDIT）评分在 13 到 38 之间，平均为 28.3 ± 9.1。与安慰剂相比，乙酸盐给药增加了双侧丘脑的 CBF（左侧：51.2 比 68.8，p < 0.001；右侧：53.7 比 69.6，p = 0.001），以及小脑、脑干和皮质。年龄较大和 AUDIT 评分较高与乙酸盐诱导的丘脑血流增加有关。安慰剂和乙酸盐输注之间的细胞因子水平和行为测量没有差异。
这项 AUD 的初步研究表明，在酒精戒断的第一周，大脑对乙酸盐的反应因脑区而异，这种反应可能与酒精依赖的严重程度有关。
