Evidence map›Paper›PMID 31922684›Full record

ArticleWorld psychiatry : official journal of the World Psychiatric Association (WPA)2020

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment.

Robert A McCutcheon, John H Krystal, Oliver D Howes

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in World psychiatry : official journal of the World Psychiatric Association (WPA), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05890768 (The Relationship Between the Efficacy of Lumateperone and Central Glutamate and Dopaminergic Metabolism), which is not on this map. Cited by 306 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
306citing papers in PubMed, 13 pooled it
31.8field-weighted citation impact, top 1% of its field
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.

NCT05890768 phase4withdrawnnot on this mapstarted 2023, after this paper: background citation

The Relationship Between the Efficacy of Lumateperone and Central Glutamate and Dopaminergic Metabolism: A Comparison With Risperidone in First Episode Psychosis

TypeinterventionalSponsorUniversity of New MexicoRan2023 to 2024Enrolled0ConditionsPsychosisArmsLumateperone, Risperidone
3 · Its place in the literature

Who cites it

306 citing papers in PubMed, 13 syntheses or guidelines pooled it, 580 citations in OpenAlex.

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246 more citing papers are in PubMed but not listed here.

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

3 authors at 3 institutions in 2 countries.

Robert A McCutcheonInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
John H KrystalDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Oliver D HowesInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Hammersmith Hospital · GBMRC London Institute of Medical Sciences · GBNational Center for PTSD · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Medical Research Council G0700995Medical Research Council MC_U120097115Medical Research Council MR/L022176/1Medical Research Council MR/N026063/1Medical Research Council MR/N027078/1NCATS NIH HHS UL1 TR001863Wellcome Trust
6 · The paper itself

Abstract

Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly to the pathophysiology of schizophrenia. In this paper we assess research that has implicated both systems in the aetiology of this disorder. We examine evidence from post-mortem, preclinical, pharmacological and in vivo neuroimaging studies. Pharmacological and preclinical studies implicate both systems, and in vivo imaging of the dopamine system has consistently identified elevated striatal dopamine synthesis and release capacity in schizophrenia. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. Converging evidence indicates that genetic and environmental risk factors for schizophrenia underlie disruption of glutamatergic and dopaminergic function. However, while genetic influences may directly underlie glutamatergic dysfunction, few genetic risk variants directly implicate the dopamine system, indicating that aberrant dopamine signalling is likely to be predominantly due to other factors. We discuss the neural circuits through which the two systems interact, and how their disruption may cause psychotic symptoms. We also discuss mechanisms through which existing treatments operate, and how recent research has highlighted opportunities for the development of novel pharmacological therapies. Finally, we consider outstanding questions for the field, including what remains unknown regarding the nature of glutamate and dopamine function in schizophrenia, and what needs to be achieved to make progress in developing new treatments.

Indexed as

amphetamineantipsychoticscognitive symptomsD1 receptorsD2 receptorsdopaminedorsolateral prefrontal cortexGABA interneuronsglutamateketamineNMDA receptorsPsychosisschizophreniastriatum

Identifiers

PMID31922684
PMCPMC6953551
OpenAlexW2999889141

What OpenQuestion holds

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Registered trials

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.