Asch Ruth H, Hillmer Ansel T, Baldassarri Stephen R, Esterlis Irina
Department of Psychiatry, Yale University, New Haven, CT, United States.
Department of Psychiatry, Yale University, New Haven, CT, United States; Department of Radiology and Biomedical Imaging, New Haven, CT, United States.
Int Rev Neurobiol. 2023;168:265-310. doi: 10.1016/bs.irn.2022.10.007. Epub 2022 Nov 18.
The role of glutamate system in the etiology and pathophysiology of psychiatric disorders has gained considerable attention in the past two decades, including dysregulation of the metabotropic glutamatergic receptor subtype 5 (mGlu5). Thus, mGlu5 may represent a promising therapeutic target for psychiatric conditions, particularly stress-related disorders. Here, we describe mGlu5 findings in mood disorders, anxiety, and trauma disorders, as well as substance use (specifically nicotine, cannabis, and alcohol use). We highlight insights gained from positron emission tomography (PET) studies, where possible, and discuss findings from treatment trials, when available, to explore the role of mGlu5 in these psychiatric disorders. Through the research evidence reviewed in this chapter, we make the argument that, not only is dysregulation of mGlu5 evident in numerous psychiatric disorders, potentially functioning as a disease "biomarker," the normalization of glutamate neurotransmission via changes in mGlu5 expression and/or modulation of mGlu5 signaling may be a needed component in treating some psychiatric disorders or symptoms. Finally, we hope to demonstrate the utility of PET as an important tool for investigating mGlu5 in disease mechanisms and treatment response.
在过去二十年中，谷氨酸系统在精神疾病的病因学和病理生理学中的作用受到了相当大的关注，包括代谢型谷氨酸受体5（mGlu5）的失调。因此，mGlu5可能是精神疾病，特别是与应激相关疾病的一个有前景的治疗靶点。在这里，我们描述了mGlu5在情绪障碍、焦虑和创伤障碍以及物质使用（特别是尼古丁、大麻和酒精使用）方面的研究结果。我们尽可能突出正电子发射断层扫描（PET）研究获得的见解，并在有可用数据时讨论治疗试验的结果，以探讨mGlu5在这些精神疾病中的作用。通过本章回顾的研究证据，我们认为，mGlu5的失调不仅在众多精神疾病中明显，可能作为一种疾病“生物标志物”，而且通过改变mGlu5表达和/或调节mGlu5信号来使谷氨酸神经传递正常化，可能是治疗某些精神疾病或症状所需的一个组成部分。最后，我们希望展示PET作为研究mGlu5在疾病机制和治疗反应中的重要工具的效用。
