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Updated: Dec 10, 2025

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans
Published on: February 4, 2014
Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action
Yasaman Malekizadeh1, Gareth Williams2, Mark Kelson3
1College of Medicine and Health University of Exeter Medical School University of Exeter Exeter UK.
Background:
Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.
Methods:
Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository.
Results:
Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection).
Conclusions:
These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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