Evidence map›Paper›PMID 32929215›Full record

Trial reportMolecular psychiatry2021

Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals.

Anahit Mkrtchian, Jennifer W Evans, Christoph Kraus, Peixiong Yuan, Bashkim Kadriu, Allison C Nugent, Jonathan P Roiser, Carlos A Zarate

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 7 pooled it
3.8field-weighted citation impact, top 4% 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.

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

63 citing papers in PubMed, 7 syntheses or guidelines pooled it, 104 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Article
  11. Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Network localization of brain functional effects of ketamine treatment for major depression.European psychiatry : the journal of the Association of European Psychiatrists · 2026
    Article
  16. Review
  17. Intranasal (R)-ketamine modulates depression symptom and neurotransmitters-associated human brain connectivity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  18. Review
  19. Review
  20. Article

3 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

8 authors at 2 institutions in 2 countries.

Anahit MkrtchianSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. anahit.mkrtchian@nih.gov.ORCID http://orcid.org/0000-0001-9876-2852
Jennifer W EvansSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Christoph KrausSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Peixiong YuanSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Bashkim KadriuSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3809-9451
Allison C NugentSection on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Jonathan P Roiser *Neuroscience and Mental Health Group, Institute of Cognitive Neuroscience, University College London, London, UK.ORCID http://orcid.org/0000-0001-8269-1228
Carlos A Zarate *Section on the Neurobiology and Treatment of Mood Disorders, Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USUniversity College London · GB

Funding

Glutamatergic Modulators for Rapid & Sustained Antidepressant EffectZIAMH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2025
$55.0M
Intramural NIH HHS ZIA MH002857Wellcome TrustWellcome Trust 200934/Z/16/Z
6 · The paper itself

Abstract

Ketamine improves motivation-related symptoms in depression but simultaneously elicits similar symptoms in healthy individuals, suggesting that it might have different effects in health and disease. This study examined whether ketamine affects the brain's fronto-striatal system, which is known to drive motivational behavior. The study also assessed whether inflammatory mechanisms-which are known to influence neural and behavioral motivational processes-might underlie some of these changes. These questions were explored in the context of a double-blind, placebo-controlled, crossover trial of ketamine in 33 individuals with treatment-resistant major depressive disorder (TRD) and 25 healthy volunteers (HVs). Resting-state functional magnetic resonance imaging (rsfMRI) was acquired 2 days post-ketamine (final sample: TRD n = 27, HV n = 19) and post-placebo (final sample: TRD n = 25, HV n = 18) infusions and was used to probe fronto-striatal circuitry with striatal seed-based functional connectivity. Ketamine increased fronto-striatal functional connectivity in TRD participants toward levels observed in HVs while shifting the connectivity profile in HVs toward a state similar to TRD participants under placebo. Preliminary findings suggest that these effects were largely observed in the absence of inflammatory (C-reactive protein) changes and were associated with both acute and sustained improvements in symptoms in the TRD group. Ketamine thus normalized fronto-striatal connectivity in TRD participants but disrupted it in HVs independently of inflammatory processes. These findings highlight the potential importance of reward circuitry in ketamine's mechanism of action, which may be particularly relevant for understanding ketamine-induced shifts in motivational symptoms.

Indexed as

Depressive Disorder, Treatment-ResistantKetamineMajor Depressive DisorderAntidepressive AgentsDouble-Blind MethodHumansMagnetic Resonance ImagingAntidepressive AgentsKetamine

Identifiers

PMID32929215
PMCPMC8462973
OpenAlexW3086459126

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.