Evidence map›Paper›PMID 23624296›Full record

Trial reportBrain, behavior, and immunity2013

Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression.

Divya Mehta, Charles L Raison, Bobbi J Woolwine, Ebrahim Haroon, Elisabeth B Binder, Andrew H Miller, Jennifer C Felger

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Brain, behavior, and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00463580 (An Evaluation of the Efficacy of the Tumor Necrosis Factor-alpha Antagonist Infliximab in Treatment Resistant Major Depression), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 13% 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.

NCT00463580 phase4completednot on this map

An Evaluation of the Efficacy of the Tumor Necrosis Factor-alpha Antagonist Infliximab in Treatment Resistant Major Depression: Mechanisms and Mediators

TypeinterventionalSponsorEmory UniversityRan2008 to 2011Enrolled60ConditionsDepressionArmsInfliximab, Placebo
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Genetic Contributions of Inflammation to Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017
    Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Article
  10. Advancing an Inflammatory Subtype of Major Depression.The American journal of psychiatry · 2025
    Review
  11. Article
  12. Article
  13. Glycolytic metabolism: Food for immune cells, fuel for depression?Brain, behavior, & immunity - health · 2024
    Article
  14. Review
  15. Annual Research Review: Neuroimmune network model of depression: a developmental perspective.Journal of child psychology and psychiatry, and allied disciplines · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 3 institutions in 2 countries.

Divya MehtaMax Planck Institute of Psychiatry, Munich, Germany.
Charles L Raison
Bobbi J Woolwine
Ebrahim Haroon
Elisabeth B Binder
Andrew H Miller
Jennifer C Felger
Emory University · USMax Planck Institute of Psychiatry · DEUniversity of Arizona · US

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Gregory B. Lesinski · 2009 to 2026
$47.5M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025008 · NCRR · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2007 to 2011
$29.0M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
X LINKED NYSTAGMUS SYNDROME WITH FEATURES OF ALBINISMM01RR000039 · NCRR · EMORY UNIVERSITY · PI LAWLEY, THOMAS JOSEPH · 1985 to 2007
$21.3M
Phenotyping Major Depression with Increased InflammationR01MH087604 · NIMH · EMORY UNIVERSITY · PI MILLER, ANDREW H · 2010 to 2014
$2.2M
Dynamics of Inflammation and its Blockade on Motivational Circuitry in DepressionR01MH108605 · NIMH · EMORY UNIVERSITY · PI TREADWAY, MICHAEL TILGHMAN · 2016 to 2020
$2.1M
Inflammation Effects on Corticostriatal Connectivity and Reward: Role of DopamineR01MH109637 · NIMH · EMORY UNIVERSITY · PI FELGER, JENNIFER C · 2016 to 2019
$2.1M
MR SPECTROSCOPY TO REVEAL CNS MECHANISMS OF CYTOKINE-INDUCED BEHAVIORAL CHANGEK23MH091254 · NIMH · EMORY UNIVERSITY · PI HAROON, EBRAHIM · 2010 to 2014
$883k
Neurobiological and Behavioral Effects of Cytokine Antagonism in Major DepressionR21MH077172 · NIMH · EMORY UNIVERSITY · PI RAISON, CHARLES · 2008 to 2009
$379k
Predictors and Targets of Response to Cytokine Antagonism in DepressionR03MH100273 · NIMH · EMORY UNIVERSITY · PI MILLER, ANDREW H · 2013 to 2014
$156k
NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR002378NCI NIH HHS P30 CA138292NCRR NIH HHS M01 RR000039NCRR NIH HHS M01 RR0039NCRR NIH HHS UL1 RR025008NIMH NIH HHS R01 MH087604NIMH NIH HHS R01 MH108605NIMH NIH HHS R01 MH109637NIMH NIH HHS R03 MH100273NIMH NIH HHS R21MH0771172NIMH NIH HHS R21 MH077172
6 · The paper itself

Abstract

The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5 mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6 h, 24 h, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2-fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6 h and 24 h after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation.

Indexed as

AdultAntibodies, MonoclonalAntidepressive AgentsCarbohydrate MetabolismDepressive Disorder, Treatment-ResistantDouble-Blind MethodFemaleGene Expression ProfilingGlucoseHumansInfliximabLipid MetabolismMaleMiddle AgedTreatment OutcomeTumor Necrosis Factor-alphaAntibodies, MonoclonalAntidepressive AgentsGlucoseInfliximabTumor Necrosis Factor-alpha

Identifiers

PMID23624296
PMCPMC3673885
OpenAlexW2054093295

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.