Evidence map›Paper›PMID 33658605›Full record

Trial reportMolecular psychiatry2021

Peripheral inflammatory biomarkers define biotypes of bipolar depression.

Yena Lee, Rodrigo B Mansur, Elisa Brietzke, Dimitrios Kapogiannis, Francheska Delgado-Peraza, Justin J Boutilier, Timothy C Y Chan, Nicole E Carmona, Joshua D Rosenblat, JungGoo Lee and 13 more

Open access · greenAbstract 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 25 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 5 pooled it
2.3field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 5 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Pooled it
  5. Secondary Mania induced by TNF-α inhibitors: A systematic review.Psychiatry and clinical neurosciences · 2022
    Pooled it
  6. Trial
  7. Trial
  8. Review
  9. Article
  10. Article
  11. The Gut Microbiota Affects Anti-TNF Responsiveness by Activating the NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  12. Article
  13. Article
  14. Review
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  20. Extracellular Vesicles in Mental Disorders: A State-of-art Review.International journal of biological sciences · 2023
    Review
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

23 authors at 14 institutions in 5 countries.

Yena LeeMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. yenalee.lee@utoronto.ca.ORCID http://orcid.org/0000-0003-0629-9456
Rodrigo B MansurMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Elisa BrietzkeDepartment of Psychiatry, School of Medicine, Queen's University, Kingston, ON, Canada.
Dimitrios KapogiannisLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2181-3118
Francheska Delgado-PerazaLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0201-0248
Justin J BoutilierDepartment of Industrial and Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Timothy C Y ChanDepartment of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-4128-1692
Nicole E CarmonaDepartment of Psychology, Ryerson University, Toronto, ON, Canada.
Joshua D RosenblatMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
JungGoo LeeDepartment of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea.
Vladimir MaleticDepartment of Neuropsychiatry and Behavioral Sciences, University of South Carolina School of Medicine, Greer, SC, USA.
Maj VinbergDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Hillerød, Denmark.ORCID http://orcid.org/0000-0002-5982-1335
Trisha SuppesDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Benjamin I GoldsteinInstitute of Medical Science, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-0340-349X
Arun V RavindranInstitute of Medical Science, University of Toronto, Toronto, ON, Canada.
Valerie H TaylorInstitute of Medical Science, University of Toronto, Toronto, ON, Canada.
Sahil ChawlaLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD, USA.
Carlos Nogueras-OrtizLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD, USA.
Victoria E CosgroveDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nicole E KramerDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Roger HoDepartment of Psychological Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0001-9629-4493
Charles A RaisonSchool of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-6687-0066
Roger S McIntyreMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
National Institutes of Health · USUniversity Health Network · CAStanford University · USUniversity of Toronto · CAUniversity of Wisconsin–Madison · USCentre for Addiction and Mental Health · CAInje University · KRNational University of Singapore · SGQueen's University · CAToronto Metropolitan University · CAUniversity of Calgary · CAUniversity of Copenhagen · DKUniversity of South Carolina · USVA Palo Alto Health Care System · US

Funding

ALZHEIMERS RESEARCH PROJECT / CLINICAL PROJECT: Mechanistic and clinical studies in Alzheimer's disease and related disordersZIAAG000975 · NATIONAL INSTITUTE ON AGING · 2025 to 2025
$1.1M
Intramural NIH HHS ZIA AG000975
6 · The paper itself

Abstract

We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r

Indexed as

Bipolar DisorderBiomarkersHumansInfliximabInsulin Receptor Substrate ProteinsMAP Kinase Signaling SystemNF-kappa BTumor Necrosis Factor-alphaBiomarkersInfliximabInsulin Receptor Substrate ProteinsIRS1 protein, humanNF-kappa BTumor Necrosis Factor-alpha

Identifiers

PMID33658605
PMCPMC8413393
OpenAlexW3134618529

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.