Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Mol Psychiatry. 2022 Aug;27(8):3223-3236. doi: 10.1038/s41380-022-01594-8. Epub 2022 May 4.
Alcohol misuse and alcohol use disorder (AlUD) have neurobiological consequences. This meta-analysis of proton magnetic resonance spectroscopy (MRS) studies aimed to assess the differences in brain metabolite levels in alcohol misuse and AUD relative to controls (PROSPERO registration: CRD42020209890). Hedge's g with random-effects modeling was used. Sub-group and meta-regression techniques explored potential sources of demographic and MRS parameter heterogeneity. A comprehensive literature review identified 43 studies, resulting in 69 models across gray and white matter (GM, WM). Lower N-acetylaspartate levels were found in frontal, anterior cingulate cortex (ACC), hippocampal, and cerebellar GM, and frontal and parietal WM, suggesting decreased neuronal and axonal viability. Lower choline-containing metabolite levels (all metabolites contributing to choline peak) were found in frontal, temporal, thalamic, and cerebellar GM, and frontal and parietal WM, suggesting membrane alterations related to alcohol misuse. Lower creatine-containing metabolite levels (Cr; all metabolites contributing to Cr peak) were found in temporal and occipital cortical GM, while higher levels were noted in midbrain/brainstem GM; this finding may have implications for using Cr as an internal reference. The lack of significant group differences in glutamate-related levels is possibly related to biological and methodological complexities. The few studies reporting on GABA found lower levels restricted to the ACC. Confounding variables were age, abstinence duration, treatment status, and MRS parameters (echo time, quantification type, data quality). This first meta-analysis of proton MRS studies consolidates the numerous individual studies to identify neurometabolite alterations within alcohol misuse and AUD. Future studies can leverage this new formalized information to investigate treatments that might effectively target the observed disturbances.
酒精滥用和酒精使用障碍（AlUD）具有神经生物学后果。本项质子磁共振波谱（MRS）研究的荟萃分析旨在评估与对照组相比，酒精滥用和 AUD 患者的脑代谢物水平差异（PROSPERO 注册：CRD42020209890）。使用具有随机效应建模的 Hedge's g。亚组和荟萃回归技术探索了人口统计学和 MRS 参数异质性的潜在来源。全面的文献综述确定了 43 项研究，共涉及灰质和白质（GM、WM）的 69 个模型。在前额、前扣带皮层（ACC）、海马和小脑 GM 以及额顶 WM 中发现 N-乙酰天冬氨酸水平降低，提示神经元和轴突活力降低。在前额、颞叶、丘脑和小脑 GM 以及额顶 WM 中发现胆碱含量代谢物水平降低（胆碱峰的所有代谢物），提示与酒精滥用相关的膜改变。在颞叶和枕叶皮质 GM 中发现肌酸含量代谢物（Cr 峰的所有代谢物）水平降低，而在中脑/脑干 GM 中发现水平升高；这一发现可能对使用 Cr 作为内参有影响。谷氨酸相关水平无显著组间差异可能与生物学和方法学的复杂性有关。少数报告 GABA 的研究发现，仅限于 ACC 的水平降低。混杂变量包括年龄、戒断时间、治疗状况和 MRS 参数（回波时间、定量类型、数据质量）。这是质子 MRS 研究的第一项荟萃分析，将众多的单独研究整合在一起，以确定酒精滥用和 AUD 中的神经代谢物改变。未来的研究可以利用这些新的规范化信息来研究可能有效针对观察到的干扰的治疗方法。
