I'm still working on this, if anyone has any contributions please post:D.
A collection of the evidence and possible treatments.
Anxiety
The role of glutamate in anxiety and related disorders.
Human clinical drug trials have demonstrated the efficacy of glutamatergic drugs for the treatment of obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia. Recent data from magnetic resonance imaging studies provide an additional link between the glutamate system and anxiety. Collectively, the data suggest that future studies on the mechanism of and clinical efficacy of glutamatergic agents in anxiety disorders are appropriately warranted.
High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam.
Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.
Advances in the Treatment of Anxiety: Targeting Glutamate
Recently, however, the neurobiological literature has shown a convergence of findings focusing on the glutamatergic system in anxiety disorders, and the growth of pharmacological tools targeting these receptors has led to the development of novel treatments having anxiolytic effects in humans and animals alike. Additionally, as this system is showing promise as a final common pathway in the pathogenesis of anxiety disorders, we may be able to employ glutamate-specific neuroimaging techniques (e.g., N-acetyl-aspartate, GLX) to both guide treatment decisions and present reliable objective biomarkers for treatment efficacy.
Depression
Emerging role of glutamate in the pathophysiology of major depressive disorder.
Accumulating evidence suggests that the glutamatergic system plays an important role in the neurobiology and treatment of this disease. Some clinical studies have demonstrated that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant patients with MDD.
Glutamate and depression: clinical and preclinical studies.
Further, there is also evidence implicating disturbances in glutamate metabolism, NMDA, and mGluR1,5 receptors in depression and suicidality. Finally, recent data indicate that a single intravenous dose of an NMDA receptor antagonist is sufficient to produce sustained relief from depressive symptoms.
The NMDA receptor as a therapeutic target in major depressive disorder.
Drugs that target the NMDA receptor have shown antidepressant properties in both clinical and preclinical studies.
The involvement of glutamate in the pathophysiology of depression.
Converging lines of evidence indicate that the glutamatergic system might be a promising target for a novel antidepressant therapy. Both ionotropic glutamate receptor ligands (functional NMDA receptor antagonists and AMPA receptor potentiators) and compounds acting at metabotropic glutamate receptors (mGluRs; group I mGluR antagonists, group II antagonists and group III agonists) produce antidepressant-like activity in several preclinical and some clinical studies.
Glutamate-based antidepressants: 20 years on.
This announcement closely follows a report that another NR2B antagonist, traxoprodil (CP 101 606), has antidepressant effects in patients unresponsive to a serotonin selective reuptake inhibitor, as well as reports of rapid and sustained antidepressant effects following a single injection of the NMDA antagonist ketamine. Here we describe evidence that glutamate-based therapies might represent an effective alternative to biogenic-amine-based agents for depression and provide perspectives on the development of these agents.
Obsessive-Compulsive Disorder
Glutamatergic Synaptic Dysfunction and Obsessive-Compulsive Disorder
In recent years, multiple lines of evidence have implicated glutamatergic synaptic dysfunction within the cortico-striatal-thalamo-cortical (CSTC) brain circuit in the etiology of OCD and related disorders, thereby prompting intensified effort in the development and evaluation of agents that modulate glutamatergic neurotransmission for the treatment of OCD. With this in mind, here we review the following topics with respect to synaptic dysfunction and the neural circuitry underlying OCD: (1) evidence supporting the critical involvement of the CSTC circuit, (2) genetic studies supporting the involvement of glutamatergic dysfunction, (3) insights from genetic animal models of OCD, and (4) preliminary findings with glutamatergic neurotransmission-modulating agents in the treatment of OCD.
Glutamatergic dysfunction--newer targets for anti-obsessional drugs.
Multiple lines of evidence point toward glutamatergic dysfunction being related to the pathophysiology of OCD, with glutamate modulating drugs being an alternative pharmacological strategy for treating OCD.
Glutamate and psychiatric disorders
Although the glutamatergic system is highly complex, there is increasing evidence for its involvement in a wide variety of symptoms seen in neuropsychiatric disorders and for the clinical potential of glutamatergic agents. It would appear from the available evidence that there are three main strands emerging. First, that hypofunction of the NMDA receptor system might be involved in the core symptoms of schizophrenia, perhaps by increasing activity in some non-NMDA systems and/or by a direct effect on dopaminergic neurotransmission. Second, that hyperfuntion in non-NMDA systems might underlie some of the more florid positive symptoms in psychotic disorders. And third, that metabotropic glutamatergic receptors might play an important role in anxiety disorders.
