Maraone A, Tarsitani L, Pinucci I, Pasquini M. Antiglutamatergic agents for obsessive-compulsive disorder: Where are we now and what are possible future prospects? World J Psychiatr 2021; 11(9): 568-580 [PMID: 34631461 DOI: 10.5498/wjp.v11.i9.568]
Corresponding Author of This Article
Massimo Pasquini, MD, PhD, Associate Professor, Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, Rome 00185, Lazio, Italy. massimo.pasquini@uniroma1.it
Research Domain of This Article
Psychiatry
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatr. Sep 19, 2021; 11(9): 568-580 Published online Sep 19, 2021. doi: 10.5498/wjp.v11.i9.568
Antiglutamatergic agents for obsessive-compulsive disorder: Where are we now and what are possible future prospects?
Annalisa Maraone, Lorenzo Tarsitani, Irene Pinucci, Massimo Pasquini
Annalisa Maraone, Lorenzo Tarsitani, Irene Pinucci, Massimo Pasquini, Department of Human Neurosciences, Sapienza University of Rome, Rome 00185, Lazio, Italy
Author contributions: Maraone A performed the majority of the writing, prepared the table; Tarsitani L and Pinucci I provided the input in writing the paper; Pasquini M designed the outline and coordinated the writing of the paper.
Conflict-of-interest statement: There is nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Massimo Pasquini, MD, PhD, Associate Professor, Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, Rome 00185, Lazio, Italy. massimo.pasquini@uniroma1.it
Received: March 1, 2021 Peer-review started: March 1, 2021 First decision: July 15, 2021 Revised: July 25, 2021 Accepted: August 6, 2021 Article in press: August 6, 2021 Published online: September 19, 2021 Processing time: 197 Days and 23.8 Hours
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.
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.
