Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK.
Psychopharmacology (Berl). 2021 May;238(5):1241-1254. doi: 10.1007/s00213-019-05344-7. Epub 2019 Sep 5.
Proton magnetic resonance spectroscopy (H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including glutamate and GABA. This non-invasive method has promise in developing centrally acting drugs, as it can be performed repeatedly within-subjects and be used to translate findings from the preclinical to clinical laboratory using the same imaging biomarker.
This review focuses on the utility of single-voxel H-MRS in developing novel glutamatergic or GABAergic drugs for the treatment of psychiatric disorders and includes research performed in rodent models, healthy volunteers and patient cohorts.
Overall, these studies indicate that H-MRS is able to detect the predicted pharmacological effects of glutamatergic or GABAergic drugs on voxel glutamate or GABA concentrations, although there is a shortage of studies examining dose-related effects. Clinical studies have applied H-MRS to better understand drug therapeutic mechanisms, including the glutamatergic effects of ketamine in depression and of acamprosate in alcohol dependence. There is an emerging interest in identifying patient subgroups with 'high' or 'low' brain regional H-MRS glutamate levels for more targeted drug development, which may require ancillary biomarkers to improve the accuracy of subgroup discrimination.
Considerations for future research include the sensitivity of single-voxel H-MRS in detecting drug effects, inter-site measurement reliability and the interpretation of drug-induced changes in H-MRS metabolites relative to the known pharmacological molecular mechanisms. On-going technological development, in single-voxel H-MRS and in related complementary techniques, will further support applications within CNS drug discovery.
质子磁共振波谱（H-MRS）是一种跨物种神经影像学技术，可测量包括谷氨酸和 GABA 在内的几种脑代谢物的浓度。这种非侵入性方法在开发中枢作用药物方面具有潜力，因为它可以在同一成像生物标志物的基础上在个体内重复进行，并用于将临床前研究结果转化为临床实验室。
本综述重点介绍单体素 H-MRS 在开发新型谷氨酸能或 GABA 能药物治疗精神疾病方面的应用，包括在啮齿动物模型、健康志愿者和患者队列中进行的研究。
总的来说，这些研究表明 H-MRS 能够检测到谷氨酸能或 GABA 能药物对体素谷氨酸或 GABA 浓度的预期药理学作用，尽管缺乏研究剂量相关作用。临床研究已经应用 H-MRS 来更好地了解药物治疗机制，包括氯胺酮在抑郁症中的谷氨酸能作用和安非他酮在酒精依赖中的作用。人们越来越关注识别脑区域 H-MRS 谷氨酸水平“高”或“低”的患者亚组，以便更有针对性地开发药物，这可能需要辅助生物标志物来提高亚组区分的准确性。
未来研究的考虑因素包括单体素 H-MRS 检测药物作用的敏感性、站点间测量的可靠性以及相对于已知药理学分子机制，解释 H-MRS 代谢物诱导的变化。单体素 H-MRS 及相关互补技术的持续技术发展将进一步支持中枢神经系统药物发现中的应用。
