Evidence map›Paper›PMID 41759687›Full record

Trial reportBrain, behavior, and immunity2026

Effects of 6-months of SSRI use on DNA-methylation and gene expression in blood.

Lauren F Barker, Allan F McRae, Hok Pan Yuen, Anjali K Henders, Leanne M Wallace, Tian Lin, Ella Davyson, Christina Phassouliotis, Jessica Spark, Melissa Kerr and 6 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Brain, behavior, and immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

16 authors.

Lauren F BarkerInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia. Electronic address: lauren.barker@uq.edu.au.
Allan F McRaeInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia.
Hok Pan YuenOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Anjali K HendersInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia.
Leanne M WallaceInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia.
Tian LinInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia.
Ella DavysonDivision of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Christina PhassouliotisOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Jessica SparkOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Melissa KerrOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Rebekah StreetOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Enda M ByrneChild Health Research Centre, The University of Queensland, Saint Lucia, Queensland, Australia.
G Paul AmmingerOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Barnaby NelsonOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Naomi R WrayInstitute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia; Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address: naomi.wray@uq.edu.au.
Patrick D McGorryOrygen, 35 Poplar Rd, Parkville, VIC 3052, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.

Funding

Building the Evidence Base for Adaptive Treatment Sequences in Clinical High RiskU01MH105258 · NIMH · ORYGEN YOUTH HEALTH RESEARCH CENTRE · PI MCGORRY, PATRICK · 2015 to 2019
$6.0M
NIMH NIH HHS U01 MH105258
6 · The paper itself

Abstract

backgroundSelective serotonin reuptake inhibitors (SSRIs) are a recommended first line medication for the treatment of major depressive disorder, due to higher tolerability and lower risk of adverse effects than other antidepressants. The mechanisms by which SSRIs reduce depressive symptoms are not well understood, but are hypothesised to include direct effects on serotonin signalling and synaptic remodelling, and indirect effects on inflammation. Indirect or off-target effects may be detectable in blood and can be investigated using methylome- and transcriptome-wide approaches.

methodsThe Staged Treatment in Early Psychosis (STEP) clinical trial included a 6-month long randomised, placebo-controlled trial of the SSRI fluoxetine in a cohort of young people at ultra-high risk for psychosis. A methylome-wide association study (MWAS; N

resultsFour methylation CpGs (cg26253898, cg09719563, cg22216017, cg26017656) were significantly associated with SSRI exposure (FDR < 0.1, 2 CpGs at FDR < 0.05) and annotated to genes involved in glucose metabolism, synaptic remodelling and inflammation (GCG, COL23A1, PEG10, SGCE, MFGE8). Gene-set enrichment analyses of genes annotated to the top 100 CpGs identified significant tissue-specific enrichments in artery, adipose and spleen tissues, and in the 'postsynaptic density' GO term. No genes were differentially expressed, including genes annotated to the significant methylation CpGs.

conclusionsMedium-term SSRI use during the STEP trial was associated with changes in DNA-methylation that may partially explain the potential antidepressant mechanisms and adverse effects of SSRIs, however replication in other cohorts is necessary to establish if these changes are generalisable to SSRI use more broadly.

Indexed as

DNA MethylationPsychotic DisordersSelective Serotonin Reuptake InhibitorsAdolescentAdultAntidepressive AgentsCpG IslandsFemaleFluoxetineGene ExpressionGenome-Wide Association StudyHumansMajor Depressive DisorderMaleYoung AdultAntidepressive AgentsFluoxetineSelective Serotonin Reuptake InhibitorsantidepressantsClinical trialDNA-methylationGCGGene expressionInflammationSSRI

Identifiers

PMID41759687
PMCPMC13313880

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Registered trials

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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.