Animal studies have reported the brain glutamatergic dysfunction in substance dependence. However, proton magnetic resonance spectroscopy (¹H-MRS) studies of glutamate in substance-dependent patients published contradicting results. In order to investigate the characteristics of brain glutamatergic alterations in substance-dependent patients, we conducted systematic reviews and meta-analyses of ¹H-MRS studies that have investigated the glutamate, glutamine, and Glx (glutamate + glutamine) concentration in substance-dependent patients. Multiple databases were searched until Sep 10, 2020. Twenty-nine studies comprising 982 patients and 787 controls were included. There was significantly decreased glutamate level in dorsolateral prefrontal cortex in patients compared with controls. Higher glutamate levels in medial prefrontal cortex and basal ganglia region were also demonstrated in patients compared with controls. Subgroup analyses based on the substance type and abstinence period (short vs medium-term abstinence period) were performed. The results revealed Glx and glutamate concentrations in all investigated brain regions were not different in patients with any types of substance dependence compared with controls. The abstinence period had no effect on the glutamate levels. In summary, substance dependence is associated with glutamatergic dysfunction of prefrontal cortex and basal ganglia. Present findings partially support the hypothesis that addiction is associated with abnormal brain glutamatergic neurotransmission.

动物研究报告了物质依赖中的脑谷氨酸能功能障碍。然而，对物质依赖患者中谷氨酸的质子磁共振波谱 ( ¹ H-MRS) 研究发表了相互矛盾的结果。为了研究物质依赖患者脑谷氨酸能改变的特征，我们对¹H-MRS 研究调查了物质依赖患者的谷氨酸、谷氨酰胺和 Glx（谷氨酸 + 谷氨酰胺）浓度。在 2020 年 9 月 10 日之前搜索了多个数据库。 包括 982 名患者和 787 名对照者在内的 29 项研究被纳入。与对照组相比，患者背外侧前额叶皮层的谷氨酸水平显着降低。与对照组相比，患者的内侧前额叶皮层和基底神经节区域的谷氨酸水平更高。进行了基于物质类型和禁欲期（短期与中期禁欲期）的亚组分析。结果显示，与对照组相比，任何类型的物质依赖患者的所有研究大脑区域的 Glx 和谷氨酸浓度都没有差异。禁欲期对谷氨酸水平没有影响。总之，物质依赖与前额叶皮层和基底神经节的谷氨酸能功能障碍有关。目前的研究结果部分支持成瘾与异常脑谷氨酸能神经传递相关的假设。