Evidence map›Paper›PMID 39333502›Full record

ArticleTranslational psychiatry2024

Longitudinal changes in DNA methylation associated with clozapine use in treatment-resistant schizophrenia from two international cohorts.

Amy L Gillespie, Emma M Walker, Eilis Hannon, Grant A McQueen, Kyra-Verena Sendt, Alessia Avila, John Lally, Cynthia Okhuijsen-Pfeifer, Marte van der Horst, Alkomiet Hasan and 10 more

Abstract read
In one paragraph

Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Trial
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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

20 authors.

Amy L Gillespie *Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK. amy.gillespie@psych.ox.ac.uk.ORCID 0000-0003-4640-699X
Emma M Walker *Department of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, UK.ORCID 0000-0003-2222-4577
Eilis HannonDepartment of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, UK.ORCID 0000-0001-6840-072X
Grant A McQueenDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Kyra-Verena SendtDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Alessia AvilaDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
John LallyDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Cynthia Okhuijsen-PfeiferDepartment of Psychiatry, University Medical Center, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-9649-3879
Marte van der HorstDepartment of Psychiatry, University Medical Center, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-5090-4137
Alkomiet HasanDepartment of Psychiatry, Psychotherapy and Psychosomatics, University of Augsburg, Augsburg, Germany.
Emma L DempsterDepartment of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, UK.ORCID 0000-0003-1257-5314
Joe BurrageDepartment of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, UK.
Jan BogersMental health Organization Rivierduinen, Leiden, The Netherlands.ORCID 0000-0001-7273-0027
Dan CohenDepartment of Community Mental Health Care, MHO North-Holland North, Heerhugowaard, The Netherlands.
Marco P BoksDepartment of Psychiatry, University Medical Center, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-6163-7484
David A CollierSGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Alice EgertonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2939-064X
Jurjen J LuykxDepartment of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands.ORCID 0000-0002-6439-2774
Jonathan MillDepartment of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, UK.ORCID 0000-0003-1115-3224
James H MacCabeDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-6754-1018

Funding

EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health) 279227RCUK | Medical Research Council (MRC) Grant MR/L003988/1RCUK | Medical Research Council (MRC) MR/K013807/1RCUK | Medical Research Council (MRC) MR/M008924/1RCUK | Medical Research Council (MRC) MR/R005176/1Universitair Medisch Centrum Utrecht (UMC Utrecht) H-150
6 · The paper itself

Abstract

The second-generation antipsychotic clozapine is used as a medication for treatment-resistant schizophrenia. It has previously been associated with epigenetic changes in pre-clinical rodent models and cross-sectional studies of treatment-resistant schizophrenia. Cross-sectional studies are susceptible to confounding, however, and cannot disentangle the effects of diagnosis and medication. We therefore profiled DNA methylation in sequential blood samples (n = 126) from two independent cohorts of patients (n = 38) with treatment-resistant schizophrenia spectrum disorders who commenced clozapine after study enrolment and were followed up for up to six months. We identified significant non-linear changes in cell-type proportion estimates derived from DNA methylation data - specifically B-cells - associated with time on clozapine. Mixed effects regression models were used to identify changes in DNA methylation at specific sites associated with time on clozapine, identifying 37 differentially methylated positions (DMPs) (p < 5 × 10

Indexed as

Antipsychotic AgentsClozapineDNA MethylationSchizophrenia, Treatment-ResistantAdultCohort StudiesEpigenesis, GeneticFemaleHumansLongitudinal StudiesMaleMiddle AgedSchizophreniaAntipsychotic AgentsClozapine

Identifiers

PMID39333502
PMCPMC11436797

What Socratic holds

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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.