Evidence map›Paper›PMID 40176389›Full record

ArticleActa neuropsychiatrica2025

Escitalopram alters tryptophan metabolism, plasma lipopolysaccharide, and the inferred functional potential of the gut microbiome in deer mice showing compulsive-like rigidity.

Larissa Karsten, Brian H Harvey, Dan J Stein, Benjamín Valderrama, Thomaz F S Bastiaanssen, Gerard Clarke, John F Cryan, Rencia van der Sluis, Heather Jaspan, Anna-Ursula Happel and 1 more

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Article in Acta neuropsychiatrica, 2025. 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

11 authors.

Larissa KarstenCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
Brian H HarveyCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
Dan J SteinSAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Benjamín ValderramaAPC Microbiome Ireland, University College Cork, Cork, Ireland.
Thomaz F S BastiaanssenAPC Microbiome Ireland, University College Cork, Cork, Ireland.
Gerard ClarkeAPC Microbiome Ireland, University College Cork, Cork, Ireland.
John F CryanAPC Microbiome Ireland, University College Cork, Cork, Ireland.
Rencia van der SluisBiomedical and Molecular Metabolism Research (BioMMet), North-West University, Potchefstroom, South Africa.
Heather JaspanDepartment of Pathology, University of Cape Town, Cape Town, South Africa.
Anna-Ursula HappelDepartment of Pathology, University of Cape Town, Cape Town, South Africa.
De Wet WolmaransCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.ORCID https://orcid.org/0000-0002-3440-4869

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveCompulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to KYN, which may contribute to hyposerotonergia, is bolstered by inflammation and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, that is, large nest building (LNB) in deer mice (

methodsTwenty-four (24) normal nest building (NNB) and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota-derived lipopolysaccharide (LPS) and its binding protein (lipopolysaccharide binding protein), and stool samples for microbial DNA.

resultsLNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB was associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.

conclusionsThese findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.

Indexed as

CitalopramCompulsive BehaviorEscitalopramGastrointestinal MicrobiomeLipopolysaccharidesSelective Serotonin Reuptake InhibitorsTryptophanAnimalsBehavior, AnimalDisease Models, AnimalFemaleKynurenineMaleMicePeromyscusCitalopramEscitalopramKynurenineLipopolysaccharidesSelective Serotonin Reuptake InhibitorsTryptophanDeer mousemicrobiomeobsessive-compulsive disorderrigidityserotonin

Identifiers

PMID40176389
PMCPMC13130255

What Socratic holds

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LicenceCC BY
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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 Socratic graph.