Evidence map›Paper›PMID 29301039›Full record

SynthesisSchizophrenia bulletin2018

Defining the Locus of Dopaminergic Dysfunction in Schizophrenia: A Meta-analysis and Test of the Mesolimbic Hypothesis.

Robert McCutcheon, Katherine Beck, Sameer Jauhar, Oliver D Howes

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Schizophrenia bulletin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 2 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

152 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Cortical 5-HTMolecular psychiatry · 2025
    Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Associations of neuromelanin in the substantia nigra with antipsychotic response in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

92 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

4 authors.

Robert McCutcheonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Katherine BeckDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Sameer JauharDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Oliver D HowesDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Funding

Medical Research Council G0700995Medical Research Council MC_U120097115Wellcome TrustWellcome Trust 094849/Z/10/ZWellcome Trust 200102/Z/15/Z
6 · The paper itself

Abstract

Background: Studies using positron emission tomography to image striatal dopamine function, have demonstrated that individuals with schizophrenia display increases in presynaptic function. Mesolimbic dysfunction specifically, has previously been suggested to underlie psychotic symptoms. This has not been directly tested in vivo, and the precise anatomical locus of dopamine dysfunction within the striatum remains unclear. The current article investigates the magnitude of dopaminergic abnormalities in individuals with schizophrenia, and determines how the magnitude of abnormality varies across functional subdivisions of the striatum. Methods: EMBASE, PsychINFO, and MEDLINE were searched from January 1, 1960, to December 1, 2016. Inclusion criteria were molecular imaging studies that had measured presynaptic striatal dopamine functioning. Effects sizes for whole striatum and functional subdivisions were calculated separately. The magnitude of difference between functional subdivisions in patients and controls was meta-analyzed. Results: Twenty-one eligible studies were identified, including 269 patients and 313 controls. Individuals with schizophrenia (Hedges' g = 0.68, P < .001) demonstrated elevated presynaptic dopamine functioning compared to controls. Seven studies examined functional subdivisions. These demonstrated significant increases in patients compared to controls in associative (g = 0.73, P = .002) and sensorimotor (g = 0.54, P = .005) regions, but not limbic (g = 0.29, P = .09). The magnitude of the difference between associative and limbic subdivisions was significantly greater in patients compared to controls (g = 0.39, P = .003). Conclusion: In individuals with schizophrenia dopaminergic dysfunction is greater in dorsal compared to limbic subdivisions of the striatum. This is inconsistent with the mesolimbic hypothesis and identifies the dorsal striatum as a target for novel treatment development.

Indexed as

NeuroimagingPositron-Emission TomographyDopamineHumansNeostriatumSchizophreniaSynapsesVentral StriatumDopamine

Identifiers

PMID29301039
PMCPMC5933516

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.