Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA; Department of Radiology, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.
Neuroimage Clin. 2022;35:103091. doi: 10.1016/j.nicl.2022.103091. Epub 2022 Jun 20.
Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (H-MRS) which is sensitive to GABA plus macromolecule signal (GABA + ). Furthermore, we examined sex differences in GABA + levels as a function of a recent history of binge drinking, given interactions between endogenous neurosteroids, GABA signaling, and alcohol. The study recruited young adult women and men (22.2 ± 2.8 years of age) who were classified as binge drinkers (BDs, N = 52) if they reported ≥ 5 binge episodes in the previous six months. Light drinkers (LDs, N = 49) reported drinking regularly, but not exceeding ≤ 2 binge episodes in the past six months. GABA-edited H-MR spectra were acquired from the occipital cortex at 3 T with the MEGA-PRESS sequence. GABA + signal was analyzed relative to water and total creatine (Cr) levels as a function of binge drinking history and sex. Controlling for within-voxel tissue composition, both GABA + indices showed decreased GABA + levels in BDs relative to LDs. The reduced GABA + concentration was associated with occasional high-intensity drinking in the BD group. This evidence is consistent with compensatory GABA downregulation that accompanies alcohol misuse, tipping the excitation/inhibition balance towards hyperexcitability. Analysis of the time course of GABA + neuroplasticity indicated that GABA + was lowest when measured one day after the last drinking occasion in BDs. While the BD vs LD differences were primarily driven by LD women, there was no interaction between Sex and a history of binge drinking. GABA + was higher in LD women compared to LD men. Aligned with the allostasis model, the mechanistic compensatory GABA downregulation observed in young emerging adults engaging in occasional binge drinking complements direct neural measures of hyperexcitability in BDs. Notably, these results suggest that neuroadaptation to alcohol is detectable at the levels of consumption that are within a normative range, and may contribute to adverse health outcomes.
binge drinking 是指一种饮酒模式，其导致血液中的酒精浓度达到或超过法定醉酒水平。它在年轻人中很常见，并且与随着饮酒量增加而增加的健康风险有关。急性醉酒通过增强 γ-氨基丁酸 (GABA) 介导的抑制作用，并通过降低兴奋性谷氨酰胺能效应，通过复杂的信号机制抑制神经活动。主要基于动物研究的证据表明，在习惯性大量使用的情况下，大脑会对急性抑制作用进行代偿。这些神经适应性变化反映在神经兴奋性过高方面，表现为戒断症状。然而，人类关于 GABA 信号代偿性降低的证据很少。本研究采用质子磁共振波谱（H-MRS）评估该机制模型的神经化学方面，该方法对 GABA 加大分子信号（GABA + ）敏感。此外，我们研究了性别差异，以评估最近的 binge drinking 史对 GABA + 水平的影响，因为内源性神经甾体、GABA 信号和酒精之间存在相互作用。本研究招募了年轻的成年女性和男性（22.2 ± 2.8 岁），如果他们报告在过去六个月中发生≥5 次 binge drinking 发作，则将其归类为 binge drinkers（BDs，N = 52）。轻饮者（LDs，N = 49）报告定期饮酒，但过去六个月中不超过 2 次 binge drinking 发作。在 3T 下使用 MEGA-PRESS 序列从枕叶皮层采集 GABA 编辑的 H-MR 光谱。根据 binge drinking 史和性别，相对于水和总肌酸（Cr）水平分析 GABA + 信号。控制体素内组织成分，BDs 中的 GABA + 指数均显示 GABA + 水平低于 LDs。在 BD 组中，BDs 中 GABA + 浓度的降低与偶尔高剂量饮酒有关。这一证据与酒精滥用伴随的 GABA 下调代偿一致，使兴奋/抑制平衡向过度兴奋倾斜。对 GABA + 神经可塑性的时程分析表明，BDs 在最后一次饮酒后一天测量时 GABA + 最低。虽然 BD 与 LD 的差异主要由 LD 女性驱动，但性别与 binge drinking 史之间没有相互作用。与 LD 男性相比，LD 女性的 GABA + 更高。与适应模型一致，在偶尔 binge drinking 的年轻新兴成年人中观察到的 GABA 代偿性下调，补充了 BD 中直接神经兴奋性过高的测量。值得注意的是，这些结果表明，在处于正常范围的消费水平下，可以检测到对酒精的神经适应，并且可能导致不良的健康后果。
