Krystal J H, Sanacora G, Blumberg H, Anand A, Charney D S, Marek G, Epperson C N, Goddard A, Mason G F
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Mol Psychiatry. 2002;7 Suppl 1:S71-80. doi: 10.1038/sj.mp.4001021.
Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.
谷氨酸和γ-氨基丁酸（GABA）系统正逐渐成为治疗情绪障碍药物的开发靶点。越来越多的临床前和临床证据表明，抗抑郁药物直接或间接降低N-甲基-D-天冬氨酸谷氨酸受体功能。降低谷氨酸能活性或谷氨酸受体相关信号转导的药物也可能具有抗躁狂作用。最近采用磁共振波谱的研究还表明，单相抑郁而非双相抑郁与皮质GABA水平降低有关。抗抑郁和心境稳定剂治疗似乎也能提高皮质GABA水平，并改善情绪障碍患者的GABA缺乏。现有证据表明，谷氨酸能和GABA能调节可能是现有抗抑郁和心境稳定剂的重要特性。未来需要开展研究，以开发和评估针对特定谷氨酸和GABA受体靶点的新型药物，用于治疗情绪障碍。
