Evidence mapPaperPMID 41804256Full record

SynthesisCNS spectrums2026

Effect of ketamine on reward processing in depressive disorders: a systematic review of neuroimaging studies.

Halima Faisal, Gia Han Le, Angela T H Kwan, Sabrina Wong, Will Cheung, Christine E Dri, Bing Cao, Taeho Greg Rhee, Stavroula Bargiota, Heidi K Y Lo and 3 more

Abstract readSystematic Review
In one paragraph

Synthesis in CNS spectrums, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Halima FaisalBachelor of Medical Sciences, Department of Schulich Medicine and Dentistry, Western University, London, ON, Canada.
Gia Han LeInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Angela T H KwanCentre for Addiction and Mental Health, Toronto, ON, Canada.
Sabrina WongBrain and Cognition Discovery Foundation, Toronto, ON, Canada.
Will CheungBrain and Cognition Discovery Foundation, Toronto, ON, Canada.
Christine E DriBrain and Cognition Discovery Foundation, Toronto, ON, Canada.
Bing CaoFaculty of Psychology, Southwest University, Chongqing, China.ORCID 0000-0001-5963-2676
Taeho Greg RheeDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Stavroula BargiotaDepartment of Psychiatry, University of Thessaly, Larissa, Greece.ORCID 0000-0002-0828-0647
Heidi K Y LoDepartment of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong.
Bianca ShenDepartment of Health Sciences, Queen's University, Kingston, ON, Canada.
Hernan F Guillen-BurgosPontificia Universidad Javeriana, Department of Psychiatry and Mental Health, Bogotá, DC, Colombia.ORCID 0000-0003-1835-431X
Roger S McIntyreDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-4733-2523

Funding

Examining Intensive Outpatient Programs as a Potential Mechanism to Reduce Suicide Risk During the Post-Hospitalization Period Among Medicaid RecipientsR01MH131528 · YALE UNIVERSITY · 2025 to 2025
$692k
NIA NIH HHS R01 AG028847NIA NIH HHS R21 AG070666NIA NIH HHS R21 AG078972NIDA NIH HHS R21 DA057540NIMH NIH HHS R01 MH131528
6 · The paper itself

Abstract

backgroundAnhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants. Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear. We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for anhedonia.

methodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched Ovid Embase/MEDLINE/PsycINFO, Cochrane Library, Scopus, Web of Science, and Google Scholar. Eligible studies included adults with MDD receiving ketamine or esketamine and undergoing fMRI, PET, or related imaging during rest or reward/emotion tasks. Thirteen studies met inclusion criteria (N = 623; 482 MDD/TRD, 141 controls), mostly randomized, double-blind, and placebo-controlled; no eligible esketamine neuroimaging studies were identified.

resultsIntravenous ketamine (typically 0.5 mg/kg over 40 min) was associated with short-term modulation of fronto-striatal and limbic networks. Resting-state fMRI commonly showed altered ventral striatal-prefrontal/ACC connectivity and broader DMN/salience/executive network reorganization across acute-to-subacute windows (≈2-48 h), with some effects changing at later follow-up (≈10 days). Task-based fMRI showed altered ventral striatal/putaminal responses during reward anticipation/feedback and modulation of medial prefrontal/cingulate activity during emotion processing. PET findings suggested increased prefrontal-cingulate metabolism and region-specific 5-HT₁B binding/availability changes, with baseline ventral striatal 5-HT₁B measures associated with symptom profiles and symptom change.

conclusionsKetamine is associated with rapid reconfiguration of reward-related circuitry, but few studies directly measured anhedonia; findings likely reflect broader reward-processing and antidepressant-associated mechanisms. Larger longitudinal multimodal studies are needed to validate biomarkers and durability.

Indexed as

Antidepressive AgentsBrainKetamineMajor Depressive DisorderRewardAnhedoniaHumansNeuroimagingAntidepressive AgentsKetamineAnhedoniadepressionglutamateketamineplasticityrewardtherapeutics

Identifiers

PMID41804256
PMCPMC13287819

What Socratic holds

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Registered trials

None linked

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 Socratic graph.