Early effects of a novel 5-HT<sub>4</sub>R agonist (PF-04995274) and the SSRI citalopram on emotional cognition in unmedicated depression: RESTAND study.
The 5 matches · 1 of them tie a paragraph to a whole file, not to given lines: a weak match, whose lines are not tinted
- [1] § Results › On a neuroimaging measure of emotional cognition, participants who received the 5-HT4 agonist showed a distinct pattern of neural changes to those on citalopram, with increased medial-fronta ↔ Emotional Cognition paper scripts/06_fmri_wholebrain_clusters.R, lines 1–80 · score 0.80 · middle temporal gyrus, angular gyrus, fusiform gyrus, lateral occipital, cerebellum, clusters
- [2] § Methods › Clinical assessment and questionnaire measures ↔ Emotional Cognition paper scripts/02_demographic_comparison.R, the whole file · a weak match · score 0.67 · Trait Anxiety, anhedonic symptoms, Inventory, STAI, depression, baseline
- [3] § Methods › Statistical analysis › Magnetic Resonance Imaging Data ↔ Emotional Cognition paper scripts/07_ROI_analysis.R, lines 417–490 · score 0.62 · medial frontal cortex, BOLD signal change, ROI, amygdala, placebo, citalopram
- [4] § Methods › Clinical assessment and questionnaire measures ↔ Emotional Cognition paper scripts/09_selfreport.R, lines 1–52 · score 0.58 · anhedonic symptoms, research visits, PANAS, VAS, STAI, depression
- [5] § Results › After one week, participants given either PF-04995274 or citalopram showed significant decreases in depressive symptoms › Self-reported symptoms and affect ↔ Emotional Cognition paper scripts/09_selfreport.R, lines 1–52 · score 0.51 · depressive symptoms, state anxiety, BDI, STAI, visit
Paper
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The authors' code
R · 266 lines · 10 KB · no license · 2 matches
09_selfreport.R, no license · at the source
Overview
- University Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
- Institute for Mental Health, University of Birmingham, Edgbaston, Birmingham, UK
- Department of Physics and Computational Radiology, Oslo University Hospital, Norway
- Faculty of Medicine, University of Oslo
Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are limited by inadequate response in a significant proportion of patients, slow onset, minimal cognitive benefit, and side effects. Preclinical studies suggest selective serotonin 4 receptor (5-HT4R) agonists may produce faster antidepressant effects via distinct mechanisms, however there has been no experimental research in clinical populations to date.
Aims: To test whether the novel 5-HT4R partial agonist PF-04995274 produces early behavioural and neural changes in emotional cognition similar to SSRIs in patients with unmedicated major depressive disorder (MDD).
Method: In a double-blind, placebo-controlled trial, 90 participants with MDD were randomised to 7 days of PF-04995274 (15 mg), citalopram (20 mg), or placebo. Emotional processing was assessed using a behavioural facial expression recognition task and fMRI of implicit emotional face processing (days 6–9). Observer- and self-reported symptoms of depression were also measured at baseline and study end.
Results: As anticipated, citalopram reduced relative accuracy and increased relative reaction time to identify negative faces, with corresponding changes in neural activity (reduced left amygdala activation to emotional faces and valence-specific shifts in cortical regions). In contrast, PF-04995274 produced no change in behavioural negative bias or amygdala activity but increased medial-frontal cortex activation across valences. While this was not a clinical trial, both active treatments demonstrated an early treatment response with reduced observer-rated depression severity relative to placebo; PF-04995274 also reduced self-reported depression, state anxiety, and negative affect.
Conclusions: PF-04995274 did not show the typical antidepressant profile of negative bias reductions observed with citalopram. Instead, it was associated with distinct increased medial-frontal activation during an emotional faces task, coupled with preliminary evidence of early clinical improvement, suggesting a potential alternative pathway for antidepressant effects. Findings support further clinical trials of 5-HT4R agonists and investigation of pro-cognitive and mood effects.
Clinicaltrials.gov registration number: NCT03516604.
Data set information: Analysis scripts and anonymised behavioural data are available on OSF.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
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Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
- 27 September 2026: the link answers (HTTP 200)
16 files, to read at the source
This repository has no license: its authors keep all rights. Read it at the source.
- Emotional Cognition paper scripts/
01_setup.R — R, 113 lines, not shown here - Emotional Cognition paper scripts/
02_demographic_compariso — R, 32 lines, 1 match, not shown heren.R - Emotional Cognition paper scripts/
03_FERT_setup_transforms — R, 252 lines, not shown here.R - Emotional Cognition paper scripts/
04_FERT_analysis.R — R, 271 lines, not shown here - Emotional Cognition paper scripts/
05_fmri_behav_faces.R — R, 71 lines, not shown here - Emotional Cognition paper scripts/
06_fmri_wholebrain_clust — R, 680 lines, 1 match, not shown hereers.R - Emotional Cognition paper scripts/
07_ROI_analysis.R — R, 490 lines, 1 match, not shown here - Emotional Cognition paper scripts/
08_HAMD_analysis.R — R, 184 lines, not shown here - Emotional Cognition paper scripts/
09_selfreport.R — R, 266 lines, 2 matches, not shown here - Emotional Cognition paper scripts/
10_sideeffects_publicati — R, 584 lines, not shown hereon.R - Emotional Cognition paper scripts/
11_ECAT_EREC_EMEM.R — R, 227 lines, not shown here - Emotional Cognition paper scripts/
12_FDOT.R — R, 60 lines, not shown here - Emotional Cognition paper scripts/
13_EPS.R — R, 221 lines, not shown here - Emotional Cognition paper scripts/
14_PILT_basics.R — R, 90 lines, not shown here - OMT analysis_forpublication.
R — R, 598 lines, not shown here - RESTAND AVLT ANALYSIS_forpublication.
Rmd — R, 706 lines, not shown here
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Data
Datasets cited
- zenodo:6107724 — at Zenodo; found in the text, “Neuroimaging measure of emotional cognition”
Versions
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Version 2, 28 September 2026
- Publisher: — → Cambridge University Press
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, pages, dates, 11 authors, 5 keywords, 2 funders, 45 references.
Cite
This paper
Gillespie, A., de Cates, A., Scaife, J., Blandhol, M., Martens, M., Gibson, D., Godlewska, B., Howard, W., Cowen, P., Murphy, S., & Harmer, C. (2026). Early effects of a novel 5-HT&
BibTeX
@article{gillespie2026ea
author = {Gillespie, A.L. and de Cates, A.N. and Scaife, J. and Blandhol, M. and Martens, M.A.G. and Gibson, D and Godlewska, B.R and Howard, W and Cowen, P.J. and Murphy, S.E. and Harmer, C.J.},
title = {{Early effects of a novel 5-HT\&
journal = {The British journal of psychiatry : the journal of mental science},
year = {2026},
month = may,
pages = {1--10},
publisher = {Cambridge University Press},
issn = {0007-1250},
doi = {10.1192/
url = {https://
pmid = {42204761},
pmcid = {PMC7619257}
}
RIS
TY - JOUR
AU - Gillespie, A.L.
AU - de Cates, A.N.
AU - Scaife, J.
AU - Blandhol, M.
AU - Martens, M.A.G.
AU - Gibson, D
AU - Godlewska, B.R
AU - Howard, W
AU - Cowen, P.J.
AU - Murphy, S.E.
AU - Harmer, C.J.
TI - Early effects of a novel 5-HT&
T2 - The British journal of psychiatry : the journal of mental science
J2 - Br J Psychiatry
PY - 2026
DA - 2026/
SP - 1
EP - 10
SN - 0007-1250
PB - Cambridge University Press
DO - 10.1192/
UR - https://
LA - en
ER -
CSL-JSON
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