The metabotropic glutamatergic receptor subtype 5 (mGluR5) may represent a promising therapeutic target for stress-related psychiatric disorders. Here, we describe mGluR5 findings in stress disorders, particularly major depressive disorder (MDD), highlighting insights from positron emission tomography studies. Positron emission tomography studies report either no differences or lower mGluR5 in MDD, potentially reflecting MDD heterogeneity. Unlike the rapidly acting glutamatergic agent ketamine, mGluR5-specific modulation has not yet shown antidepressant efficacy in MDD and bipolar disorder. Although we recently showed that ketamine may work, in part, through significant mGluR5 modulation, the specific role of mGluR5 downregulation in ketamine's antidepressant response is unclear. In contrast to MDD, there has been much less investigation of mGluR5 in bipolar disorder, yet initial studies indicate that mGluR5-specific treatments may aid in both depressed and manic mood states. The direction of modulation needed may be state dependent, however, limiting clinical feasibility. There has been relatively little study of posttraumatic stress disorder or obsessive-compulsive disorder to date, although there is evidence for the upregulation of mGluR5 in these disorders. However, while antagonism of mGluR5 may reduce fear conditioning, it may also reduce fear extinction. Therefore, studies are needed to determine the role mGluR5 modulation might play in the treatment of these conditions. Further challenges in modulating this prevalent neurotransmitter system include potential induction of significant side effects. As such, more research is needed to identify level and type (positive/negative allosteric modulation or full antagonism) of mGluR5 modulation required to translate existing knowledge into improved therapies.

中文翻译：

---

mGluR5 和应激障碍：从受体成像研究中获得的知识

代谢型谷氨酸能受体亚型 5 (mGluR5) 可能代表与压力相关的精神疾病的有希望的治疗靶点。在这里，我们描述了 mGluR5 在应激障碍中的发现，特别是重度抑郁症 (MDD)，突出了正电子发射断层扫描研究的见解。正电子发射断层扫描研究报告 MDD 中没有差异或 mGluR5 较低，这可能反映了 MDD 的异质性。与快速作用的谷氨酸能药物氯胺酮不同，mGluR5 特异性调节尚未在 MDD 和双相情感障碍中显示出抗抑郁功效。尽管我们最近表明氯胺酮可能在一定程度上通过显着的 mGluR5 调节起作用，但 mGluR5 下调在氯胺酮抗抑郁反应中的具体作用尚不清楚。与 MDD 相比，在双相情感障碍中对 mGluR5 的研究要少得多，但初步研究表明 mGluR5 特异性治疗可能有助于抑郁和躁狂情绪状态。所需的调制方向可能取决于状态，但是，限制了临床可行性。迄今为止，对创伤后应激障碍或强迫症的研究相对较少，尽管有证据表明 mGluR5 在这些疾病中上调。然而，虽然 mGluR5 的拮抗作用可能会减少恐惧条件反射，但它也可能会减少恐惧消退。因此，需要进行研究以确定 mGluR5 调节在这些疾病的治疗中可能发挥的作用。调节这种普遍的神经递质系统的进一步挑战包括潜在的显着副作用的诱导。因此，