Antiglutamatergic agents for obsessive-compulsive disorder: Where are we now and what are possible future prospects?

Abstract

Recent data suggest that obsessive-compulsive disorder (OCD) is driven by an imbalance among the habit learning system and the goal-directed system. The frontostriatal loop termed cortico-striatal-thalamo-cortical (CSTC) circuitry loop is involved in habits and their dysfunction plays an important role in OCD. Glutamatergic neurotransmission is the principal neurotransmitter implicated in the CSTC model of OCD. Hyperactivity in the CSTC loop implies a high level of glutamate in the cortical-striatal pathways as well as a dysregulation of GABAergic transmission, and could represent the pathophysiology of OCD. Moreover, the dysregulation of glutamate levels can lead to neurotoxicity, acting as a neuronal excitotoxin. The hypothesis of a role of neurotoxicity in the pathophysiology of OCD clinically correlates to the importance of an early intervention for patients. Indeed, some studies have shown that a reduction of duration of untreated illness is related to an earlier onset of remission. Although robust data supporting a progression of such brain changes are not available so far, an early intervention could help interrupt damage from neurotoxicity. Moreover, agents targeting glutamate neurotransmission may represent promising therapeutical option in OCD patients.

Keywords: Obsessive-compulsive disorder; Antiglutamatergic agents; Glutammate; Early intervention; Neurophysiopathology; Duration of untreated illness

Core Tip: In pathophysiology of obsessive-compulsive disorder (OCD), dysfunction of the cortico-striatal-thalamo-cortical (CSTC) loop could provoke an imbalance between goal-directed system and habit learning system. Glutamate is the principal neurotransmitter implicated in the CSTC model of OCD. Glutammate dysregulation and neurotoxicity seem to be correlated, thus, an early intervention and a reduction of duration of untreated illness appear central in treatment of OCD, as well as the use of glutamate-modulating drugs that could help to interrupt damage from neurotoxicity.