Evidence map›Paper›PMID 35977861›Full record

ArticleBiological psychiatry2022

Contribution of the Opioid System to the Antidepressant Effects of Fluoxetine.

Elena Carazo-Arias, Phi T Nguyen, Marley Kass, Hyun Jung Jee, Katherine M Nautiyal, Valerie Magalong, Lilian Coie, Valentine Andreu, Mark M Gergues, Huzefa Khalil and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 16 citations in OpenAlex.

  1. AiScience · 2026
    Article
  2. Article
  3. Review
  4. Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024
    Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 3 countries.

Elena Carazo-AriasDepartment of Biological Sciences, Columbia University, New York State Psychiatric Institute, New York, New York; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
Phi T NguyenDepartment of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
Marley KassDepartment of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
Hyun Jung JeeDivision of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
Katherine M NautiyalDepartment of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire.
Valerie MagalongProgram in Developmental Neurogenetics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California.
Lilian CoieDepartment of Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York.
Valentine AndreuDepartment of Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York.
Mark M GerguesDepartment of Psychology, Rutgers University, New Brunswick, New Jersey.
Huzefa KhalilMolecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
Huda AkilMolecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
Danusa Mar ArcegoDepartment of Psychiatry, Faculty of Medicine, Douglas Hospital Research Centre, McGill University, Montreal, Québec, Canada.
Michael MeaneyDepartment of Psychiatry, Faculty of Medicine, Douglas Hospital Research Centre, McGill University, Montreal, Québec, Canada; Sackler Program for Epigenetics and Psychobiology, Douglas Hospital Research Centre, McGill University, Montreal, Québec, Canada; Singapore Institute for Clinical Sciences, Singapore.
Christoph AnackerDepartment of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York.
Benjamin A SamuelsDepartment of Psychology, Rutgers University, New Brunswick, New Jersey.
John E PintarDepartment of Neuroscience & Cell Biology, Rutgers University, New Brunswick, New Jersey.
Irina MorozovaCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York State Psychiatric Institute, New York, New York; Department of Chemical Engineering, Columbia University, New York State Psychiatric Institute, New York, New York.
Sergey KalachikovCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York State Psychiatric Institute, New York, New York; Department of Chemical Engineering, Columbia University, New York State Psychiatric Institute, New York, New York; Data Science Institute, Columbia University, New York State Psychiatric Institute, New York, New York.
Rene HenDepartment of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York; Department of Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York; Department of Pharmacology, Columbia University, New York State Psychiatric Institute, New York, New York; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York. Electronic address: rh95@cumc.columbia.edu.
New York Psychoanalytic Society and Institute · USRutgers, The State University of New Jersey · USDouglas Mental Health University Institute · CAUniversity of Michigan · USChildren's Hospital of Los Angeles · USDartmouth College · US

Funding

Investigating the role of Bmp4 in glial subtype specification and temperamentU01DA043098 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUDA AKIL, Jun Li · 2017 to 2026
$6.9M
Effect of Major Depression and antidepressants on human neurogenesisR01MH083862 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI BOLDRINI, MAURA, HEN, RENE · 2009 to 2018
$5.4M
Cellular Mechanisms of Antidepressant ActionR37MH068542 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI HEN, RENE · 2008 to 2017
$4.1M
Diverse Roles of Adult Dentate Gyrus NeurogenesisR01NS081203 · NINDS · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI SCHARFMAN, HELEN E · 2013 to 2017
$1.8M
Hippocampal neurogenesis, pattern separation & age-related cognitive impairments.R01AG043688 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FENTON, ANDRE ANTONIO, HEN, RENE · 2013 to 2017
$1.6M
Endogenous opioid system contributions to anti-depressant actionR21MH116462 · NIMH · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI HEN, RENE, PINTAR, JOHN E · 2018 to 2019
$455k
Health Promotion in a Yup'ik Community: Improving Health Through CollaborationR21HL083862 · NHLBI · UNIVERSITY OF ALASKA FAIRBANKS · PI LARDON, CECILE SABINE · 2007 to 2008
$401k
HSRD VA CDP 13-003NHLBI NIH HHS R21 HL083862NIA NIH HHS R01 AG043688NIDA NIH HHS U01 DA043098NIMH NIH HHS R01 MH083862NIMH NIH HHS R21 MH116462NIMH NIH HHS R37 MH068542NINDS NIH HHS R01 NS081203
6 · The paper itself

Abstract

backgroundSelective serotonin reuptake inhibitors such as fluoxetine have a limited treatment efficacy. The mechanism by which some patients respond to fluoxetine while others do not remains poorly understood, limiting treatment effectiveness. We have found the opioid system to be involved in the responsiveness to fluoxetine treatment in a mouse model for anxiety- and depressive-like behavior.

methodsWe analyzed gene expression changes in the dentate gyrus of mice chronically treated with corticosterone and fluoxetine. After identifying a subset of genes of interest, we studied their expression patterns in relation to treatment responsiveness. We further characterized their expression through in situ hybridization and the analysis of a single-cell RNA sequencing dataset. Finally, we behaviorally tested mu and delta opioid receptor knockout mice in the novelty suppressed feeding test and the forced swim test after chronic corticosterone and fluoxetine treatment.

resultsChronic fluoxetine treatment upregulates proenkephalin expression in the dentate gyrus, and this upregulation is associated with treatment responsiveness. The expression of several of the most significantly upregulated genes, including proenkephalin, is localized to an anatomically and transcriptionally specialized subgroup of mature granule cells in the dentate gyrus. We have also found that the delta opioid receptor contributes to some, but not all, of the behavioral effects of fluoxetine.

conclusionsThese data indicate that the opioid system is involved in the antidepressant effects of fluoxetine, and this effect may be mediated through the upregulation of proenkephalin in a subpopulation of mature granule cells.

Indexed as

Analgesics, OpioidFluoxetineAnimalsAntidepressive AgentsCorticosteroneMiceMice, KnockoutReceptors, Opioid, deltaSelective Serotonin Reuptake InhibitorsAnalgesics, OpioidAntidepressive AgentsCorticosteroneFluoxetineReceptors, Opioid, deltaSelective Serotonin Reuptake InhibitorsDentate gyrusDepressionEnkephalinFluoxetineOpioidSelective serotonin reuptake inhibitors (SSRI)

Identifiers

PMID35977861
PMCPMC10426813
OpenAlexW4282946854

What OpenQuestion 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 OpenQuestion graph.