Evidence map›Paper›PMID 36890661›Full record

ArticleBipolar disorders2023

Use of a gene expression signature to identify trimetazidine for repurposing to treat bipolar depression.

Chiara C Bortolasci, Srisaiyini Kidnapillai, Briana Spolding, Trang T T Truong, Timothy Connor, Courtney Swinton, Bruna Panizzutti, Zoe S J Liu, Andrew Sanigorski, Olivia M Dean and 20 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bipolar disorders, 2023. 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
3.3field-weighted citation impact, top 8% 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.

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, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Past, present and future of research on brain energy metabolism in bipolar disorder.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025
    Article
  5. Article
  6. Trimetazidine Improves Mitochondrial Dysfunction in SOD1International journal of molecular sciences · 2024
    Article
  7. Article
  8. 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

30 authors at 7 institutions in 3 countries.

Chiara C BortolasciIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Srisaiyini KidnapillaiIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Briana SpoldingIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Trang T T TruongIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.ORCID 0000-0001-9301-5911
Timothy ConnorIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Courtney SwintonIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Bruna PanizzuttiIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.ORCID 0000-0002-8825-734X
Zoe S J LiuIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Andrew SanigorskiIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Olivia M DeanIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.ORCID 0000-0002-2776-3935
Tamsyn CrowleyIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Mark RichardsonBioinformatics Core Research Facility (BCRF), Deakin University, Geelong, Australia.
Kiymet BozaogluMurdoch Children's Research Institute, Parkville, Victoria, Australia.
Katerina VlahosMurdoch Children's Research Institute, Parkville, Victoria, Australia.
Stephanie CowderyIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Brad WatmuffIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Stephan F SteynCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
De Wet WolmaransCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
Barend J EngelbrechtCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
Christina PerryThe Florey Institute of Neuroscience and Mental Health, Parkville, Australia.
Katherine DrummondThe Florey Institute of Neuroscience and Mental Health, Parkville, Australia.
Terence PangThe Florey Institute of Neuroscience and Mental Health, Parkville, Australia.ORCID 0000-0002-7000-5304
Stéphane JamainUniv Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, Créteil, France.ORCID 0000-0002-4321-4100
Laura GrayIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Sean L McGeeIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Brian H HarveyCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.ORCID 0000-0002-9864-7894
Jee Hyun KimIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Marion LeboyerUniv Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, Créteil, France.
Michael BerkIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
Ken WalderIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.ORCID 0000-0002-6758-4763
Deakin University · AUFlorey Institute of Neuroscience and Mental Health · AUNorth-West University · ZAInserm · FRMurdoch Children's Research Institute · AUSouth African Medical Research Council · ZAThe University of Melbourne · AU

Funding

National Health and Medical Research Council 1156072National Health and Medical Research Council GNT1078928National Health and Medical Research Council GNT1153607
6 · The paper itself

Abstract

objectivesThe aim of this study was to repurpose a drug for the treatment of bipolar depression.

methodsA gene expression signature representing the overall transcriptomic effects of a cocktail of drugs widely prescribed to treat bipolar disorder was generated using human neuronal-like (NT2-N) cells. A compound library of 960 approved, off-patent drugs were then screened to identify those drugs that affect transcription most similar to the effects of the bipolar depression drug cocktail. For mechanistic studies, peripheral blood mononuclear cells were obtained from a healthy subject and reprogrammed into induced pluripotent stem cells, which were then differentiated into co-cultured neurons and astrocytes. Efficacy studies were conducted in two animal models of depressive-like behaviours (Flinders Sensitive Line rats and social isolation with chronic restraint stress rats).

resultsThe screen identified trimetazidine as a potential drug for repurposing. Trimetazidine alters metabolic processes to increase ATP production, which is thought to be deficient in bipolar depression. We showed that trimetazidine increased mitochondrial respiration in cultured human neuronal-like cells. Transcriptomic analysis in induced pluripotent stem cell-derived neuron/astrocyte co-cultures suggested additional mechanisms of action via the focal adhesion and MAPK signalling pathways. In two different rodent models of depressive-like behaviours, trimetazidine exhibited antidepressant-like activity with reduced anhedonia and reduced immobility in the forced swim test.

conclusionCollectively our data support the repurposing of trimetazidine for the treatment of bipolar depression.

Indexed as

Bipolar DisorderTrimetazidineAnimalsDisease Models, AnimalDrug RepositioningHumansLeukocytes, MononuclearRatsTranscriptomeTrimetazidinebipolar depressiondrug repurposinggene expression signaturetrimetazidine

Identifiers

PMID36890661
PMCPMC10946906
OpenAlexW4323652221

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.