The DOI matches its Crossref record; 227 of the 229 references it cites were found in a registry or an index.
Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment
Open accessAbstract
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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“structural abnormalities in CSTC circuits involving orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and striatum have been repeatedly demonstrated in OCD 51–53.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [51]
In the citing paper
“The role of this glutamate transporter gene in OCD is also supported by the observation that the anti-glutamatergic drug riluzole can be beneficial in the treatment of OCD and by the finding of elevated glutamate levels in the CSF of OCD patients (Pittenger et al. 2011).”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Pittenger et al. 2011
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“Studies using neurochemical and neuroimaging methods have shown that various neurotransmitters are implicated in the pathophysiology of this disorder, including serotonin [1], dopamine [2] and glutamate [3].”
From P300 and delay-discounting in obsessive–compulsive disorder (2022) · cites this paper as [3]
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Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391
Diagnostic and Statistical Manual of Mental Disorders.
Widiger, T. A. (2000) · Oxford University Press eBooks · doi:10.1037/10518-009 · Cited by 19,766
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,227
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766
The Synaptic Organization of the Brain
(2004) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195159561.001.1 · Cited by 3,574
The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication
Ruscio, A. M., Stein, D. J., Chiu, W. T., & Kessler, R. C. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.94 · Cited by 2,771
Lifetime Prevalence of Specific Psychiatric Disorders in Three Sites
Robins, L. N. (1984) · Archives of General Psychiatry · doi:10.1001/archpsyc.1984.01790210031005 · Cited by 2,550
Rothstein, J. D., Dykes-Hoberg, M., Pardo, C. A., Bristol, L. A., Jin, L., Kuncl, R. W., Kanai, Y., Hediger, M. A., Wang, Y., Schielke, J. P., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80086-0 · Cited by 2,534
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Li, Z., Zhang, X., Sun, J., Ding, Y., Shen, Y., Tian, Y., Zhang, Y., Guo, H., Wei, Y., Han, S., et al. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111733
Zakariaei, Z., Hosseini, S. R., Alizadeh‐Navaei, R., Malekbala, M., Montazeri, M., Fakhar, M., & Talabaki, H. (2026) · BMC Infectious Diseases · doi:10.1186/s12879-026-13855-w
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Mohammadi, A. H., Amin, N., Tavousi, S. A., Mahabady, M. K., Aschner, M., & Mirzaei, H. (2026) · Advances in neurotoxicology · doi:10.1016/bs.ant.2026.03.001
Cheung, N. (2026) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2026.1799705
Memantine Augmentation in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis
Lyndon, S., & McNally, D. R. (2026) · CNS Drugs · doi:10.1007/s40263-026-01318-4
Animal models of obsessive-compulsive disorder
Moya, P. R., Ardiles, N. M., Henríquez-Belmar, F., Plaza-Briceño, W., & Acevedo-Hernández, P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27446-6.00008-x
Neurochemistry and neurotransmitters involved in obsessive–compulsive disorder
Grant, J., & Sohl, E. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27446-6.00004-2
Chaudhari, P. V., Awathale, S. N., Ahire, S. R., Ansari, R., Goyal, S. N., & Nakhate, K. T. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179238
Shamkhal, F. A., Moghimi, A., Kobravi, H. R., Fadardi, J. S., & al Mohaddesin, F. R. (2026) · PLoS ONE · doi:10.1371/journal.pone.0354614
The emerging landscape of circulatory biomarkers in Alzheimer’s disease
Kumari, S., Rais, A., Ashar, M. S., Singh, A. K., Anwar, M., Pradhan, R., & Dey, S. (2026) · International review of neurobiology · doi:10.1016/bs.irn.2026.08.008
Bharati, D., Khan, J., Nadar, J., Sen, N. K., Pualsa, D., & Mohite, P. B. (2026) · Toxicology International · doi:10.18311/ti/2026/v33i2/54172
Barlattani, T., Sernia, G., D’Amelio, C., Maritato, S., Gabriele, D., Bologna, A., Trebbi, F., Ricci, V., Tomasetti, C., Martiadis, V., et al. (2026) · Psychiatry International · doi:10.3390/psychiatryint7050207
Sarcosine: Investigational NMDA receptor modulator and GlyT1 inhibitor
Vadlapatla, R., Cho, Y., Shirazi, A., & Qudus, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44037-3.00319-5
Obsessive-compulsive disorder in adulthood: Etiology, diagnosis, and treatment
Voderholzer, U., Jelinek, L., Schennach, R., Domschke, K., Grabe, H. J., & Endres, D. (2026) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2026.0156
Yan, H., Han, Y., Guo, W., Guo, W., & Cao, H. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e01089
Neuroscience-informed psychoeducation for OCD
McLaughlin, N. C. R., Fedorenko, E. J., & Kulak, M. J. (2026) · Progress in brain research · doi:10.1016/bs.pbr.2026.10.002
Mak, L. E. (2014) · MacSphere (McMaster University) · doi:10.71548/23709
Metadata
- Authors
- Pittenger, C., Bloch, M. H., & Williams, K.
- Affiliations
- Yale University (US)
- Corresponding author
- Pittenger, Christopher
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 132
- Issue
- 3
- Pages
- 314-332
- ISSN
- 0163-7258 (ISSN-L)
- 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
- 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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