Cited by 367Schizophrenia research and treatmentAdvanced MRI Techniques and ApplicationsNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 79 of the 82 references it cites were found in a registry or an index.

Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

Open access

Merritt, Kate, Egerton, Alice, Kempton, Matthew J., Taylor, Matthew J., McGuire, Philip K.·2016·JAMA Psychiatry

DOI 10.1001/jamapsychiatry.2016.0442

Open this paper in CoChat — free account Open PDF

Abstract

IMPORTANCE: Alterations in glutamatergic neurotransmission may be fundamental to the pathophysiology of schizophrenia, and the glutamatergic system is a target for novel therapeutic interventions in the disorder. OBJECTIVE: To investigate the nature of brain glutamate alterations in schizophrenia by conducting a meta-analysis of glutamate proton magnetic resonance (MRS) spectroscopy studies. DATA SOURCES: The MEDLINE database was searched for studies published from January 1, 1980, to April 1, 2015. Search terms included magnetic resonance spectroscopy, schizophrenia, psychosis, clinical or genetic high risk, and schizoaffective. Inclusion criteria were single voxel 1H-MRS studies reporting glutamate, glutamine or Glx values for a patient or risk group in comparison to a healthy volunteer group. STUDY SELECTION: Fifty-nine studies were identified, which included 1686 patients and 1451 healthy individuals serving as controls. DATA EXTRACTION AND SYNTHESIS: A random-effects, inverse-weighted variance model was used to calculate the pooled effect size. Mean values were extracted and verified independently. Effect sizes were determined for glutamate, glutamine, and Glx in brain regions that had been examined in at least 3 different studies. A secondary analysis grouped studies into those examining patients at different stages of illness (high risk, first-episode psychosis, or chronic schizophrenia). Effects of age, antipsychotic dose, and symptom severity were determined using meta-regression. RESULTS: In schizophrenia, there were significant elevations in glutamate in the basal ganglia (Hedges g = 0.63; 95% CI, 0.15-1.11), glutamine in the thalamus (g = 0.56; 95% CI, 0.02-1.09), and Glx in the basal ganglia (g = 0.39; 95% CI, 0.09-0.70) and medial temporal lobe (g = 0.32; 95% CI, 0.12-0.52). No region showed a reduction in glutamate metabolites in schizophrenia. Secondary analyses revealed that elevated medial frontal Glx levels were evident in individuals at high risk for schizophrenia (g = 0.26; 95% CI, 0.05-0.46) but not in those with first-episode psychosis or chronic schizophrenia, whereas elevated Glx in the medial temporal lobe was seen with chronic schizophrenia (g = 0.40; 95% CI, 0.08-0.71) but not in the high-risk or first-episode groups. Meta-regression found no association with age, symptom severity, or antipsychotic dose. CONCLUSIONS AND RELEVANCE: Schizophrenia is associated with elevations in glutamatergic metabolites across several brain regions. This finding supports the hypothesis that schizophrenia is associated with excess glutamatergic neurotransmission in several limbic areas and further indicates that compounds that reduce glutamatergic transmission may have therapeutic potential.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1001/jamapsychiatry.2016.0442

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378
Book Reviews: Statistical Methods for Meta-Analysis Larry V. Hedges and Ingram Olkin New York: Academic Press, 1985. xxii + 369 pp
Wasserman, S. S., Hedges, L. V., & Olkin, I. (1988) · Journal of Educational Statistics · doi:10.2307/1164953 · Cited by 10,377
Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials
Sterne, J. A. C., Sutton, A. J., Ioannidis, J. P. A., Terrin, N., Jones, D. R., Lau, J., Carpenter, J., Rucker, G., Harbord, R. M., Schmid, C. H., et al. (2011) · BMJ · doi:10.1136/bmj.d4002 · Cited by 7,709
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577
Recent advances in the phencyclidine model of schizophrenia
(1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.10.1301 · Cited by 2,904
Statistical Methods for Meta-Analysis
(1985) · Elsevier eBooks · doi:10.1016/c2009-0-03396-0 · Cited by 2,570
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
Moghaddam, B., Adams, B., Verma, A., & Daly, D. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02921.1997 · Cited by 1,793
Glutamate receptor dysfunction and schizophrenia
Olney, J. W. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240016004 · Cited by 1,685
Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia
Lisman, J. E., Coyle, J. T., Green, R. W., Javitt, D. C., Benes, F. M., Heckers, S., & Grace, A. A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.005 · Cited by 1,010

Show all 82 references

Research works printed but not linked: 1

Szulc A, Galinska B, Tarasów E, et al. Glutamatergic system dysfunction in schizophrenia: a proton magnetic resonance spectroscopy ( 1 H MRS) study. Pol J Radiol. 2004;69(1):33-36.

Sorted by citations

Items 301–367 of 367

Neurometabolic patterns of an “at risk for mental disorders” syndrome involve abnormalities in the thalamus and anterior midcingulate cortex
Smesny, S., Gussew, A., Schack, S., Langbein, K., Wagner, G., & Reichenbach, J. R. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.04.021 · Cited by 2
Language-network connectivity and cortical glutamate and their associations with overweighted semantic prior beliefs, schizotypy and task-based hallucinationsPreprint
Demler, V. F., Sterner, E., & Knolle, F. (2025) · medRxiv · doi:10.64898/2025.12.07.25341628 · Cited by 2
A trifluoromethyl-regulated fluorescent probe based on a thiol–chromene "click" reaction for visualizing thiol dynamics in the brains of schizophrenia model mice
Wu, Z., Zhang, C., Guo, X., Shi, Z., Cai, B., Liu, H., Jin, M., Wang, S., Zhang, J., & Yang, Y.-T. (2025) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2025.138727 · Cited by 1
Xanomeline-Trospium for the Treatment of Schizophrenia
Ehret, M. J., & Meyer, J. M. (2025) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20250022 · Cited by 1
Glutamate, NAA, and energy metabolism in clinical high risk and first episode psychosis
King, B., Kempton, M. J., Man, S. K., Egerton, A., & Mizrahi, R. (2025) · Scientific Reports · doi:10.1038/s41598-025-22845-y · Cited by 1
“As prior evidence overall indicates a decrease in mitochondrial activity 56 and an increase in ACC glutamate metabolites 20,23 in the clinical high risk or early stages of psychosis, we hypothesised that these markers would be negatively correlated.”
Neuropharmacological targets for schizophrenia treatment: An update
de Lima, C. A. C., Barbosa, M. E. O., de Souza-Júnior, F. J. C., Farias, S. V., Fontes-Júnior, E. A., & Maia, C. D. S. F. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111580 · Cited by 1
Associations between glutamate and cerebral blood flow in treatment-resistant schizophrenia during clozapine treatment
Sun, J., Zelaya, F. O., Sendt, K.-V., McQueen, G., Gillespie, A. L., Lally, J., O’Daly, O., Lythgoe, D. J., Howes, O. D., Barker, G. J., et al. (2026) · Journal of Psychopharmacology · doi:10.1177/02698811251409141 · Cited by 1
“…reviews and meta-analyses have indicated higher Glx (glutamate plus glutamine) in the basal ganglia across the schizophrenia-spectrum disorders (Merritt et al., 2016, 2023; Nakahara et al., 2022), lower medial frontal cortex glutamatergic levels with individual differences in the degree of…”
Ketamine for negative and depressive symptoms in schizophrenia: the evidence so far
Diendorfer, C., Bum, C., Weidenauer, A., Sauerzopf, U., Bartova, L., Dajic, I., Müller, L., Rujescu, D., Praschak-Rieder, N., & Willeit, M. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1766485 · Cited by 1
“Across multiple studies, elevated Glu and Glx levels have been observed in subcortical regions such as the basal ganglia (30, 31).”
Guidelines for the prevention of psychosis from the World Federation of Societies of Biological Psychiatry (WFSBP) and EPI Canada
Solmi, M., Correll, C. U., Boldrini, T., Addington, J., Barbezat, E., Bassetto, S. A., Bechdolf, A., Devoe, D. J. A., Firth, J., Fusar‐Poli, P., et al. (2026) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2026.2651738 · Cited by 1
“The umbrella review identified 17 eligible studies (Davis et al. 2014; Dutt et al. 2015; Erickson et al. 2016; Harrisberger et al. 2016; Merritt et al. 2016; Walter et al. 2016; Ding et al. 2019; Wenneberg et al. 2020; Del Fabro et al. 2021; Jalbrzikowski et al. 2021; Baldwin et al. 2022; Luna et…”
From association to causality: mechanistic pathways linking the gut microbiome to psychiatric disorders
Almarzooqi, S., Yassin, L. K., AlNuaimi, F., Alketbi, S., Skrabulyte-Barbulescu, J., AlAhbabi, N., Alremeithi, D., Almarashda, R., Almazrouei, S., Shehab, S., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04305-x · Cited by 1
“A meta-analysis of 59 studies demonstrated elevated glutamate and related metabolites in the basal ganglia, thalamus, and medial temporal lobe, reinforcing glutamatergic dysfunction as central to pathophysiology [187].”
Glutamatergic Modulators in Schizophrenia: Are We Ready to Move Beyond the Narrow Focus on Dopamine? A Potential Paradigm Shift in Psychopharmacology
de Filippis, R., Guinart, D., Correll, C. U., Liparota, G., Kishimoto, T., & Fazio, P. D. (2026) · ALPHA PSYCHIATRY · doi:10.31083/ap52026 · Cited by 1
“…studies have consistently demonstrated elevated glutamate or glutamate-glutamine (Glx) levels in subgroups of patients with schizophrenia, particularly in the early stages of the disease, suggesting a hypergluta-matergic state that could predict response to glutamater-3 gic modulators [43,44].”
The Reality Distortion and Thought Disorganisation Dimensions
Tarsitani, L., & Maraone, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-78202-7_4 · Cited by 1
Abnormal neurobiochemical metabolites in the first- episode schizophrenia and clinical high-risk population.
Ouyang, L., Zheng, W., Ma, X., Liu, Y., He, Y., & Chen, X. (2021) · PubMed Central · doi:10.11817/j.issn.1672-7347.2021.200240 · Cited by 1
Serum concentrations of aminoacylase 1 in schizophrenia as a potential biomarker: a case-sibling-control study
Göverti, D., Yüksel, R. N., Kaya, H., Büyüklüoğlu, N., Yücel, Ç., & Göka, E. (2021) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2021.1981435 · Cited by 1
“found that there were significant elevations in glutamate in the different brain regions [27].”
Background
Blood-Brain Barrier Perturbations, Psychiatric Disorders, and New Opportunities for Refining Disease Models
Arnone, D. (2022) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2022.07.009 · Cited by 1
Relationship between cortical glutamatergic metabolite levels and hippocampal activity in schizotypy
Wang, Y.-M., Egerton, A., McMullen, K., McLaughlin, A. P., Kumari, V., Lythgoe, D. J., Barker, G. J., Williams, S., Zelaya, F. O., & Modinos, G. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2021.12.039 · Cited by 1
Glutamate, Glutamatergic Drugs and Schizophrenia
Muguruza, C., & Callado, L. F. (2022) · Springer eBooks · doi:10.1007/978-3-030-87480-3_17 · Cited by 1
Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation with cognitive functioningPreprint
Broeders, T. A. A., Bhogal, A. A., Morsinkhof, L. M., Schoonheim, M. M., Röder, C. H., Edens, M., Klomp, D. W. J., Wijnen, J. P., & Vinkers, C. H. (2021) · medRxiv · doi:10.1101/2021.02.01.21250977 · Cited by 1
Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy ControlsPreprint
Sabaroedin, K., Razi, A., Chopra, S., Tran, N., Pozaruk, A., Chen, Z.-L., Finlay, A., Nelson, B., Allott, K., Alvarez-Jimenez, M., et al. (2021) · medRxiv · doi:10.1101/2021.03.11.21253426 · Cited by 2
“In-vivo imaging findings have been mixed, with reports of increased, decreased, or no changes in prefrontal excitatory or inhibitory metabolites in FEP [26–30] and people with established schizophrenia [27, 28, 31, 32].”
Background
Erbb4 deletion from fast-spiking interneurons causes psychosis-relevant neuroimaging phenotypesPreprint
Kiemes, A., Navacerrada, M. E. S., Kim, E., Randall, K., Simmons, C., Gonzalez, L. R., Petrinovic, M. M., Lythgoe, D. J., Rotaru, D., Censo, D. D., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.07.483347 · Cited by 1
Association between increased anterior cingulate glutamate and psychotic-like symptoms, but not autistic traitsPreprint
Demler, V. F., Sterner, E., Wilson, M., Zimmer, C., & Knolle, F. (2023) · medRxiv · doi:10.1101/2023.02.01.23285183 · Cited by 1
“ACC glutamate alterations have been associated with psychotic-like experiences in healthy individuals (70), symptoms and structural changes in high-risk individuals (71), symptoms in first episode psychosis (71–73) and chronic psychosis (74).”
Background
A multistage, dual voxel study of glutamate in the anterior cingulate cortex in schizophrenia supports a primary pyramidal dysfunction model of disorganizationPreprint
Fan, L., Zhang, Z., Ma, X., Liang, L., Wang, Y., Liu, Y., Ouyang, L., Li, Z., Chen, X., Hé, Y., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.27.568930 · Cited by 1
Neurometabolic dysfunction in psychosis observed with 7 T MRSPreprint
Schallmo, M., Demro, C., Killebrew, K. W., Olman, C. A., Sponheim, S. R., & Marjańska, M. (2024) · medRxiv · doi:10.1101/2024.01.03.24300788 · Cited by 1
Magnetic Resonance Spectroscopy Gamma-Aminobutyric Acid: A Promising Biomarker for Antipsychotic Treatment?
Rowland, L. M., & Wijtenburg, S. A. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.01.004
Noninvasive Methodology (NMR)
Mehta, M. A. (2020) · Springer eBooks · doi:10.1007/978-3-319-68864-0_46
Neuroimaging and Antipsychotics
Vita, A., Schlagenhauf, F., Barlati, S., & Heinz, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-97307-4_7
P.1.07 N-methyl-D-aspartate receptor encephalitis versus schizophrenia: A comparative brain imaging study using MR spectroscopy
Bruns, M. M., Ilzarbe, D., Rosa, M., Compte, A., Castro‐Fornieles, J., Dalmau, J. O., & Sugranyes, G. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.01.010
Applications of Neuroimaging Biomarkers in CNS Drug Development
Cole, P. E., & Einstein, S. G. (2019) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-803161-2.00009-6 · Cited by 1
Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterningPreprint
Park, M. T. M., Jeon, P., KHAN, A. R., Dempster, K., Chakravarty, M. M., Lerch, J. P., Mackinley, M., Théberge, J., & Palaniyappan, L. K. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/829630
Schizophrenia and Alzheimer’s disease
Eggermont, J. J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819818-6.00006-6
Magnetic Resonance Spectroscopy Studies in Schizophrenia
Öngür, D. (2020) · Springer eBooks · doi:10.1007/978-3-030-35206-6_10
MRI in CNS Drug Development
Mehta, M. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-62351-7_10
Neuroimaging in bipolar disorder and schizophrenia
Du, G., & Öngür, D. (2022) · Oxford University Press eBooks · doi:10.1093/med/9780197574522.003.0009
Novel Approaches for Treating Psychotic Disorders
Marques, T. R., & Kapur, S. (2017) · doi:10.1093/med/9780190681425.003.0021
Neuroimaging of Psychotic Disorders
Heckers, S., Woodward, N. D., & Öngür, D. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780190681425.003.0014
Noninvasive Methodology (NMR)
Mehta, M. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-56637-5_46-1
“For example, glutamate is elevated in patients with schizophrenia (Merritt et al. 2016; Schwerk et al. 2014) and MRS would be a viable methodology to test compounds for their ability to reduce glutamate levels in vivo.”
Background
Magnetic Resonance Spectroscopy
Squarcina, L., & Brambilla, P. (2023) · Neuromethods · doi:10.1007/978-1-0716-3230-7_12
Impactul consumului de canabis asupra semnelor neurologice minore la pacienţii cu schizofrenie
Petrescu, C., Petrescu, D. M., Ciobanu, C. A., Ciobanu, A. M., & Marian, G. (2023) · Psihiatru ro · doi:10.26416/psih.73.2.2023.8255
RDoC Framework Through the Lens of Predictive Processing: Focusing on Cognitive System DomainPreprint
Banaraki, A. K., Toghi, A., & Mohammadzadeh, A. (2023) · doi:10.31219/osf.io/3f9ce
In the afterglow: Immune dysfunction in schizophrenia spectrum disorders
Gangadin, S. S. (2024) · doi:10.33612/diss.939086872
Medications for Psychosis: Dopamine Blockers and Dopamine Partial Agonists (Antipsychotics)
Uchida, H., Kim, E., Jarskog, L. F., Fleischhacker, W. W., Remington, G. J., & Lieberman, J. A. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_134
Association of abnormal cortical inhibition and clinical outcomes in patients at clinical high risk for psychosis
Wu, G., Zhu, T., Ma, C., Xu, L., Qian, Z., Kong, G., Cui, H., Zhang, T., Wang, J., & Tang, Y. (2024) · Clinical Neurophysiology · doi:10.1016/j.clinph.2024.11.015
MRI in CNS Drug Development
Mehta, M. A. (2024) · Springer eBooks · doi:10.1007/978-3-031-61992-2_14
Glutamate and Proton MR Spectroscopy in Schizophrenia
Koizumi, T., & Graff‐Guerrero, A. (2025) · Neuromethods · doi:10.1007/978-1-0716-4494-2_11
A Multimodal Observational Case-Control Study Exploring Gut Microbiota–Hippocampus Alterations in Individuals With High Positive Schizotypy From the General Population
Iseli, G. C., Vázquez-Castellanos, J., Coynel, D., Stone, J., Soler, M., Allen, P., Zelaya, F., Derrien, M., Lang, U. E., Debbané, M., et al. (2025) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2025.100567 · Cited by 1
“Similarly, human studies have found that elevated hippocampal Glu is associated with overall functioning in un-medicated patients with SZ (2,5,24) and FEP (25) and in CHR-P individuals with subsequent psychosis transition (9,26–28).”
Cannabis use and glutamate across the psychosis spectrum: in vivo evidence from 7T proton magnetic resonance spectroscopy
Roalf, D. R., Moore, T. M., Stifelman, J., Pecsok, M. K., Atkins, A., Baller, E. B., Calkins, M. E., Biasi, M. D., Kohler, C. G., Mastracchio, C., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03705-1
Meta‐analysis of 1 H‐MRS glutamate profiles in adult schizophrenia spectrum disorders and autism spectrum disorder: Study protocol
Takahashi, Y., Takamatsu, N., Okada, N., Yagishita, S., & Kasai, K. (2025) · Psychiatry and Clinical Neurosciences Reports · doi:10.1002/pcn5.70260
“After pilot testing, studies scoring 17 – 20, 13 – 16, and ≤ 12 points will be classified as low, moderate, and high risk of bias, respectively.”
Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis
Kiemes, A., Livingston, N. R., Lukow, P. B., Knight, S., Jelen, L. A., Reilly, T. J., Dima, A., Nettis, M. A., Lythgoe, D. J., Casetta, C., et al. (2025) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaf078
“11 Of note, a later meta-analysis which reviewed the ACC and the medial cingulate cortex separately based on reported voxel location found no significant Glx elevation in the ACC in CHRp groups compared to healthy controls (95% CI, − 0.03 to 0.57, P =.08), 12 highlighting that variation in ACC…”
Influential
Additional file 1 of The impact of spectral basis set composition on estimated levels of cingulate glutamate and its associations with different personality traits
Demler, V. F., Sterner, E., Wilson, M., Zimmer, C., & Knolle, F. (2024) · Figshare · doi:10.6084/m9.figshare.25698156
Cognitive Impairment in Schizophrenia: Neurobiological Bases
Martini, F., Spangaro, M., Sapienza, J., Bosia, M., & Cavallaro, R. (2025) · Comprehensive approach to psychiatry · doi:10.1007/978-3-032-06209-3_11
Unmet Promise or Missed Potential? A pairwise and network meta-analysis on efficacy and safety of metabotropic glutamate receptor agonists and positive allosteric modulators in schizophrenia
Mishra, A., Shaju, A., Ibrahimpur, N. S., Mishra, B. R., Srinivasan, A., & Maiti, R. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.01.023
Cord serum metabolic signatures associated with neonatal anthropometry and neurodevelopment through age two in twins
Hu, L., Wang, C., Yang, M., Zhu, M., Xiang, F., Song, L., Wang, Y., Mei, H., Zhou, A., & Xiao, H. (2026) · iScience · doi:10.1016/j.isci.2026.114809
Insights into changes in glutaminergic metabolites in the anterior cingulate cortex: A systematic review and meta-analysis of magnetic resonance spectroscopy in schizophrenia
Chan, M. S.-P., Tang, P.-Y., Chua, Z.-K., Cheong, W.-L., & Mok, S.-Y. (2026) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2026.112175 · Cited by 3
Associations between corticolimbic glutamatergic metabolites and functional connectivity in people at clinical high-risk for psychosisPreprint
Gee, A. L., Livingston, N. R., Kiemes, A., Knight, S., Lukow, P. B., Lythgoe, D. J., Vorontsova, N., Donocik, J. G., Davies, J., Rabiner, E. A., et al. (2026) · medRxiv · doi:10.64898/2026.04.08.26350385
267. Unsupervised Clustering of ACC and Hippocampal Metabolites Identifies Subgroups in Antipsychotic-Naïve First-Episode Psychosis
Nelson, E., Richman, J., Bashir, A., Maximo, J., & Lahti, A. C. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.03.501
Introduction to Psychoradiology: Neuroimaging Biomarkers and Their Clinical Application in Psychiatry
Ora, M., Bentley, E., Nguyen, P. T. L., Cai, Y., Vibhute, P. G., Bathla, G., Agarwal, A. K., Gupta, V., Muhleman, M., & Soni, N. (2026) · Seminars in Roentgenology · doi:10.1016/j.ro.2026.150991
Fronto-striatal neurometabolite signatures of impulsivity in early abstinence from methamphetamine
Dumitrescu, A. M., Vest, M. F., Loftis, J. M., & Murnane, K. S. (2026) · NeuroImage Clinical · doi:10.1016/j.nicl.2026.104015
“At the same time, short ‑ echo Glu + Gln quantification at 3.0 T is inherently challenging because of J ‑ coupling and overlap with neighboring resonances, and Glu + Gln estimates tend to have higher CRLB and lower precision than NAA or choline compounds (Merritt et al., 2016).”
Influential
Effects of riluzole on excitation-inhibition imbalance and functional connectivity in 22q11.2 deletion syndrome: a multimodal 7-Tesla MRI study
Sylvester, A. L., Spapens, J., Tse, D. H. Y., Serrarens, C., Kappert, S., Soons, N., Poser, B. A., Linden, D. E. J., Ivanov, D., van Amelsvoort, T., et al. (2026) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2026.112279
Group Differences of Multiregion Glutamate Concentration in Clinical High Risk and Schizophrenia
Man, S. K., Blasco, M. B., Alemi, R., Raminfard, S., Rusjan, P., Near, J., Sarpal, D. K., & Mizrahi, R. (2026) · European Journal of Neuroscience · doi:10.1111/ejn.70626
“Similarly, in CHR populations, early studies re-ported increases in medial frontal glutamatergic metabolites (Merritt et al. 2016); however, a more recent meta-analysis incorporating larger datasets and improved harmonization protocols has not found reliable group differences for glutamate or Glx…”
Influential
Metabolomics and Psychological and Mental Illness
Li, Z., Zhu, Z., Wang, D., & Zhang, H. (2026) · Springer eBooks · doi:10.1007/978-981-95-9567-9_8
Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications
Lin, K., Wang, P., Li, S., Ma, C., Wen, D., Wang, X., & Liao, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1712425
“Increased glutamate levels are observed in the thalamus, basal ganglia, and medial temporal lobe cortex (38).”
Was Kraepelin Prescient Regarding Excitation-Inhibition Imbalance in Schizophrenia?
Hinney, B., Missonnier, P., Gass, P., & Inta, D. (2026) · Schizophrenia Bulletin Open · doi:10.1093/schizbullopen/sgag032
“…g enerally show a heightened level of glutamatergic metabolites in most brain regions, contrary to what the NMDA-hypofunction model would sugg est. 41 While the authors of the corresponding meta-analysis took these results to mean that glutamatergic excitotoxicity may play a role in…”
7T magnetic resonance spectroscopic imaging of subcortical neurometabolites across antipsychotic treatment in acutely symptomatic early-phase schizophrenia spectrum disorders
Pupi, M. D., Papale, A. E., Calabro, F. J., Raminfard, S., Blazer, A., Overbey, T., Foran, W., Hetherington, H. P., Moon, C., Luna, B., et al. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02522-y
Real‐Time Neurofeedback Training to Modulate Glutamate‐Glutamine Concentration Using Functional Magnetic Resonance Spectroscopy
Wang, Z., Babu, S., Beck, N., & Frank, S. (2026) · NMR in Biomedicine · doi:10.1002/nbm.70399
“Altered glutamate-glutamine concentrations, as assessed by MRS, have been re-ported in various clinical conditions, such as dementia [38, 39], depression [40], epilepsy [41], and schizophrenia [42, 43], suggesting dysfunction in excitatory neurotransmitter-related processes.”
N-Acetylcysteine in Schizophrenia: A Convergent Redox-Based Approach to Therapeutic Potential
Rubio-Contreras, E., Pérez‐Toribio, A., Alvaro, P., Cosialls, A. M., & Morén, C. (2026) · Antioxidants · doi:10.3390/antiox15101277
Epigenetics processes involved in schizophrenia and antipsychotic treatment
MALIK, K., Davies, S. J. C., RAVINDRAN, N., & LUCA, V. D. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00024-4
Neurometabolic Differences in Psychosis Observed with 7 T Magnetic Resonance Spectroscopy
Schallmo, M., Demro, C., Killebrew, K. W., Sheldon, A. A., Olman, C. A., Sponheim, S. R., & Marjańska, M. (2026) · Schizophrenia Bulletin · doi:10.1093/schbul/sbag137
“We chose these 6 metabolites based on a review of the literature 10 , 14 , 16 – 20 , 86 – 88 prior to data analysis, which sugg ested that concentrations of these metabolites in OCC and/or PFC may be altered in PwPP.”

Authors: Merritt, K., Egerton, A., Kempton, M. J., Taylor, M. J., & McGuire, P. K.
Affiliations: King's College London (GB)
Corresponding author: Merritt, Kate
ORCID: Merritt, Kate
Egerton, Alice
Kempton, Matthew J.
Taylor, Matthew J.
McGuire, Philip K.
Venue: JAMA Psychiatry
Publisher: American Medical Association (AMA)
Published: 2016-07-01
Volume: 73
Issue: 7
Pages: 665
ISSN: 2168-622X (ISSN-L)
DOI: 10.1001/jamapsychiatry.2016.0442
OpenAlex: W2424710696
Cited by: 367
References: 82
Citations by year: 2026: 26 · 2025: 23 · 2024: 25 · 2023: 37 · 2022: 33 · 2021: 50 · 2020: 55 · 2019: 44 · 2018: 41 · 2017: 28 · 2016: 5
FWCI: 34.95
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: JAMA Psychiatry (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion, other-oa)
Funders: National Institute for Health and Care Research
King's College London
Medical Research Council (MR/L003988/1, MR/J008915/1)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: schizophrenia, glutamate, glutamine, glutamatergic neurotransmission, basal ganglia, thalamus, medial temporal lobe, medial frontal cortex, first-episode psychosis, clinical high risk for psychosis, chronic schizophrenia, schizoaffective disorder, antipsychotic dosing, symptom severity, neuroimaging biomarkers
MeSH terms: Brain, Brain Mapping, Glutamine, Humans, Synaptic Transmission, Reference Values, Risk Factors, Schizophrenia, Glutamic Acid, Genetic Predisposition to Disease, Proton Magnetic Resonance Spectroscopy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks