Cited by 426Obsessive-Compulsive Spectrum DisordersPsychoanalysis and Psychopathology ResearchAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment

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Pittenger, Christopher, Bloch, Michael H., Williams, Kyle·2011·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2011.09.006PMC PMC3205262

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Abstract

Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics.

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Authors: Pittenger, C., Bloch, M. H., & Williams, K.
Affiliations: Yale University (US)
Corresponding author: Pittenger, Christopher
ORCID: Pittenger, Christopher
Bloch, Michael H.
Williams, Kyle
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2011-12
Volume: 132
Issue: 3
Pages: 314-332
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2011.09.006
PMC: PMC3205262
OpenAlex: W2109125813
Cited by: 426
References: 229
Citations by year: 2026: 30 · 2025: 24 · 2024: 23 · 2023: 31 · 2022: 17 · 2021: 33 · 2020: 65 · 2019: 28 · 2018: 25 · 2017: 26 · 2016: 39 · 2015: 34 · 2014: 25 · 2013: 18 · 2012: 7
FWCI: 2.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R34MH083115, K08MH081190, K23MH091240, R25MH077823)
Topics: Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: obsessive-compulsive disorder, glutamate, glutamate dysregulation, treatment-refractory OCD, pathophysiology, excitatory neurotransmission, neuroimaging, animal models, cognitive behavioral therapy, pharmacotherapy
MeSH terms: Animals, Clinical Trials as Topic, Drug Evaluation, Preclinical, Humans, Neurobiology, Obsessive-Compulsive Disorder, Randomized Controlled Trials as Topic, Neurotransmitter Agents, Glutamic Acid

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Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment

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