The metabotropic glutamate receptor 5 as a biomarker for psychiatric disorders

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.