ArticleJournal of psychopharmacology (Oxford, England)2017
Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning.
Article in Journal of psychopharmacology (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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Who cites it
6 citing papers in PubMed, 16 citations in OpenAlex.
- Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.Aging and disease · 2021Article
- Lithium treatment and human hippocampal neurogenesis.Translational psychiatry · 2021Article
- Telomere length and human hippocampal neurogenesis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- A Social Media Study on the Effects of Psychiatric Medication Use.Proceedings of the ... International AAAI Conference on Weblogs and Social Media. International AAAI Conference on Weblogs and Social Media · 2019Article
- The circadian gene Nr1d1 in the mouse nucleus accumbens modulates sociability and anxiety-related behaviour.The European journal of neuroscience · 2018Article
- Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Current pharmacological treatments for major depressive disorder (MDD) are ineffective in a significant proportion of patients, and the identification of new antidepressant compounds has been difficult. 'Connectivity mapping' is a method that can be used to identify drugs that elicit similar downstream effects on mRNA levels when compared to current treatments, and thus may point towards possible repositioning opportunities. We investigated genome-wide transcriptomic changes to human hippocampal progenitor cells treated with therapeutically relevant concentrations of a tricyclic antidepressant (nortriptyline) and a selective serotonin reuptake inhibitor (escitalopram). We identified mRNA changes common to both drugs to create an 'antidepressant mRNA signature'. We used this signature to probe the Library of Integrated Network-based Cellular Signatures (LINCS) and to identify other compounds that elicit similar changes to mRNA in neural progenitor cells. Results from LINCS revealed that the tricyclic antidepressant clomipramine elicited mRNA changes most similar to our mRNA signature, and we identified W-7 and vorinostat as functionally relevant drug candidates, which may have repositioning potential. Our results are encouraging and represent the first attempt to use connectivity mapping for drug repositioning in MDD.
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Registered trials
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.