Glutamate Systems in DSM-5 Anxiety Disorders: Their Role and a Review of Glutamate and GABA Psychopharmacology

Abstract

Serotonin reuptake inhibitors and benzodiazepines are evidence-based pharmacological treatments for Anxiety Disorders targeting serotonin and GABAergic systems, respectively. Although clearly effective, these medications fail to improve anxiety symptoms in a significant proportion of patients. New insights into the glutamate system have directed attention toward drugs that modulate glutamate as potential alternative treatments for anxiety disorders. Here we summarize the current understanding of the potential role of glutamate neurotransmission in anxiety disorders and highlight specific glutamate receptors that are potential targets for novel anxiety disorder treatments. We also review clinical trials of medications targeting the glutamate system in DSM-5 anxiety disorders. Understanding the role of the glutamate system in the pathophysiology of anxiety disorder may aid in developing novel pharmacological agents that are effective in treating anxiety disorders.

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

“…The deregulation of serotonin, GABA, dopamine, and glutamate levels in the central nervous system is associated with the pathogenesis of mental health disorders like anxiety [ 111 , 112 , 113 ]. Moreover, recent studies provide evidence that the gut microbiota affects anxiety symptoms.…”

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

“…A growing body of evidence also indicates that abnormalities in glutamatergic neurotransmission play an important role in the development of many major psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder and OCD. Glutamatergic neurotransmission plays a critical role in modulating the activation of the cortico-striatal-thalamus circuitries that occur in OCD [1][2][3]. Several glutamate modulators, including memantine, topiramate and lamotrigine, have been evaluated, but they are still not approved for the treatment of OCD [1,[3][4][5][6].…”

“…Glutamatergic neurotransmission plays a critical role in modulating the activation of the cortico-striatal-thalamus circuitries that occur in OCD [1][2][3]. Several glutamate modulators, including memantine, topiramate and lamotrigine, have been evaluated, but they are still not approved for the treatment of OCD [1,[3][4][5][6]. Recent preclinical, imaging and genetic studies support a specific role for glutamatergic transmission in OCD, also opening possible perspectives in the obsessivecompulsive spectrum [6].…”

“…Glutamatergic neurotransmission plays a critical role in modulating the activation of the cortico-striatal-thalamus circuitries that occur in OCD [1][2][3]. Several glutamate modulators, including memantine, topiramate and lamotrigine, have been evaluated, but they are still not approved for the treatment of OCD [1,[3][4][5][6].…”

“…Glutamatergic neurotransmission plays a critical role in modulating the activation of the cortico-striatal-thalamus circuitries that occur in OCD [1][2][3]. Several glutamate modulators, including memantine, topiramate and lamotrigine, have been evaluated, but they are still not approved for the treatment of OCD [1,[3][4][5][6]. Ketamine, an aryl cyclohexylamine derivative synthesized in 1962, was first introduced into clinical practice as an intravenous (IV) anesthetic agent in 1970 [7].…”