Evidence map›Paper›PMID 41704530›Full record

ReviewJournal of mood and anxiety disorders2026

Reconsidering the glutamate hypothesis of obsessive-compulsive disorder: A systematic review of proton magnetic resonance spectroscopy studies in unmedicated participants.

Gabriella Restifo-Bernstein, Jia Guo, Lawrence S Kegeles, Dikoma C Shungu, Helen Blair Simpson

Abstract readReview
In one paragraph

Review in Journal of mood and anxiety disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Gabriella Restifo-BernsteinNew York State Psychiatric Institute, New York, NY, USA.
Jia GuoColumbia University, New York, NY, USA.
Lawrence S KegelesNew York State Psychiatric Institute, New York, NY, USA.
Dikoma C ShunguWeill Cornell Medicine, New York, NY, USA.
Helen Blair SimpsonNew York State Psychiatric Institute, New York, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glutamatergic dysfunction in cortico-striato-thalamo-cortical (CSTC) circuits is a hypothesized cause of obsessive-compulsive disorder (OCD). Numerous proton magnetic resonance spectroscopy (¹H MRS) studies have examined this question, yet no systematic review has been conducted in unmedicated participants with OCD. We searched PubMed, Web of Science, and Embase for ¹H MRS studies examining glutamate (Glu) and the related metabolites glutamine (Gln) and γ-aminobutyric acid (GABA), which are associated with Glu in the Glu-Gln-GABA cycle, as well as the composite measure of Glu and Gln (Glx). Twenty studies were included in this systematic review; 17 examined cross-sectional differences in metabolite levels between participants with OCD and healthy controls, 12 examined associations between metabolite levels and OCD severity, and six examined treatment-associated changes in metabolite levels. Some studies assessed multiple outcomes. Findings across these ¹H MRS studies provide limited evidence to support the glutamate hypothesis of OCD and implicate GABA instead, although further studies of glutamatergic function are needed to definitively address it. Our findings highlight the need for further research on the role of GABA in OCD, involving larger samples of unmedicated participants, advanced ¹H MRS techniques, and multimodal imaging approaches to simultaneously assess metabolite levels and function.

Indexed as

GABAGlutamateGlutamineObsessive-compulsive disorderProton magnetic resonance spectroscopy

Identifiers

PMID41704530
PMCPMC12908078

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.