Effects of Gabapentin on Dorsal Anterior Cingulate Cortex GABA and Glutamate Levels and Their Associations With Abstinence in Alcohol Use Disorder: A Randomized Clinical Trial.
Effects of Gabapentin on Dorsal Anterior Cingulate Cortex GABA and Glutamate Levels and Their Associations With Abstinence in Alcohol Use Disorder: A Randomized Clinical Trial.
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加巴喷丁对背侧前扣带皮层GABA和谷氨酸水平的影响及其与酒精使用障碍戒断的关系：一项随机临床试验。
DOI：
10.1176/appi.ajp.2021.20121757
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发表时间：
2021-09-01
影响因子：
17.7
通讯作者：
Anton, Raymond F.
中科院分区：
文献类型：
--
作者：
Prisciandaro, James J.;Hoffman, Michaela;Brown, Truman R.;Voronin, Konstantin;Book, Sarah;Bristol, Emily;Anton, Raymond F.
尽管加巴喷丁已被证明可以有效缓解酒精使用障碍 (AUD) 患者的酒精戒断症状和预防酗酒，但这些治疗效果背后的神经生物学作用机制仍然未知。本研究评估了背侧前扣带皮层 (dACC) GABA 和谷氨酸变化作为加巴喷丁治疗 AUD 的 16 周随机临床试验中的候选作用机制。 68 名患有 AUD 的成年人，包括有戒酒综合症病史，接受加巴喷丁 1200mg/d (n=37) 或安慰剂 (n=31) 治疗，并在戒酒 72 小时以上后接受 9 次医疗管理就诊。在治疗前和随机化后大约 14 天获得 dACC GABA (n=67) 和谷氨酸 (n=64) 水平的质子磁共振波谱 (1H-MRS) 估计值。禁欲天数百分比 (PDA) 通过时间线追踪访谈报告。加巴喷丁对 GABA 和谷氨酸水平的影响取决于早期治疗期间参与者的 PDA（GABA：β=−0.48，p=0.002；谷氨酸：β=1.68，p=0.005）。具体而言，加巴喷丁与以下因素相关：1) 大部分/完全戒酒的参与者中谷氨酸的增加幅度更大，GABA 水平的下降幅度更大，而 2) 第二次扫描前 1/2 天以上饮酒的参与者则相反。此外，相对于安慰剂治疗的参与者，加巴喷丁治疗的参与者在早期治疗期间谷氨酸水平增加较多，在研究的其余部分中具有更多的 PDA（β=0.30，p<0.006）。除了深入了解加巴喷丁促进 AUD 患者戒酒的机制外，本研究还提供了有效治疗生物标志物的证据，该生物标志物可用于评估其他谷氨酸和/或 GABA 能药物治疗 AUD 和相关病症。
Although gabapentin has demonstrated efficacy in mitigating alcohol withdrawal symptoms and preventing relapse drinking in individuals with Alcohol Use Disorder (AUD), the neurobiological mechanisms of action underlying these therapeutic effects remain unknown. The present study evaluated dorsal anterior cingulate cortex (dACC) GABA and glutamate changes as candidate mechanisms of action within a 16-week randomized clinical trial of gabapentin for AUD. Sixty-eight adults with AUD, including a history of Alcohol Withdrawal Syndrome, received gabapentin 1200mg/d (n=37) or placebo (n=31) and 9 medical-management visits following ≥72-hours of abstinence. Proton Magnetic Resonance Spectroscopy (1H-MRS) estimates of dACC GABA (n=67) and glutamate (n=64) levels were acquired at pretreatment and approximately 14-days post-randomization. Percent days abstinent (PDA) were reported via Timeline-Followback interview. Effects of gabapentin on GABA and glutamate levels depended on participants’ PDA during early treatment (GABA: β=−0.48, p=0.002; glutamate: β=1.68, p=0.005). Specifically, gabapentin was associated with, 1) greater increases in glutamate and greater decreases in GABA levels in participants who remained mostly/entirely abstinent, yet 2) the opposite in participants who drank >1/2 of the days preceding the second scan. Furthermore, gabapentin-treated participants with greater increases in glutamate levels during early treatment had more PDA across the remainder of the study, relative to placebo-treated participants (β=0.30, p< 0.006). In addition to providing insight into the mechanisms through which gabapentin may promote abstinence in individuals with AUD, the present study also provides evidence for a biomarker of efficacious treatment that may be used to evaluate other glutamatergic and/or GABAergic medications for AUD and related conditions.
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影响因子：
9.9
作者：
Kuzniecky, R;Ho, S;Hetherington, H
通讯作者：
Hetherington, H
影响因子：
3.2
作者：
Ende, Gabriele;Hermann, Derik;Vollstaedt-Klein, Sabine
通讯作者：
Vollstaedt-Klein, Sabine
影响因子：
39
作者：
Mason, Barbara J.;Quello, Susan;Begovic, Adnan
通讯作者：
Begovic, Adnan
影响因子：
4.1
作者：
Caputo, Fabio;Cibin, Mauro;Zoli, Giorgio
通讯作者：
Zoli, Giorgio
DOI：
10.1007/7854_2011_131
发表时间：
2013-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF ALCOHOL ADDICTION
影响因子：
--
作者：
Meyerhoff, Dieter J.;Durazzo, Timothy C.;Ende, Gabriele
通讯作者：
Ende, Gabriele