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Network analysis of gene expression in peripheral blood identifies mTOR and NF-κB pathways involved in antipsychotic-induced extrapyramidal symptoms

The Pharmacogenomics Journal volume 15, pages 452–460 (2015)Cite this article

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Abstract

To identify the candidate genes for pharmacogenetic studies of antipsychotic (AP)-induced extrapyramidal symptoms (EPS), we propose a systems biology analytical approach, based on protein–protein interaction network construction and functional annotation analysis, of changes in gene expression (Human Genome U219 Array Plate) induced by treatment with risperidone or paliperidone in peripheral blood. 12 AP-naïve patients with first-episode psychosis participated in the present study. Our analysis revealed that, in response to AP treatment, constructed networks were enriched for different biological processes in patients without EPS (ubiquitination, protein folding and adenosine triphosphate (ATP) metabolism) compared with those presenting EPS (insulin receptor signaling, lipid modification, regulation of autophagy and immune response). Moreover, the observed differences also involved specific pathways, such as anaphase promoting complex /cdc20, prefoldin/CCT/triC and ATP synthesis in no-EPS patients, and mammalian target of rapamycin and NF-κB kinases in patients with EPS. Our results showing different patterns of gene expression in EPS patients, offer new and valuable markers for pharmacogenetic studies.

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Acknowledgements

This study was supported by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS, Fondo de Investigacion Sanitaria PI10/02430) and the Catalan Innovation, Universities and Enterprise Authority (Grants DURSI 2009SGR1295, 2009SGR1501); and ‘Sara Borrell’ contract from the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS, Fondo de Investigación Sanitaria) (Grant CD09/00296) (to P.G.). The authors thank the Language Advisory Service of the University of Barcelona, Spain for manuscript revision. The authors also thank Ana Meseguer for sample collection assistance.

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Authors and Affiliations

  1. Department Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain

    S Mas, P Gassó, E Parellada & A Lafuente

  2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    S Mas, P Gassó, E Parellada, M Bernardo & A Lafuente

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain

    S Mas, E Parellada, M Bernardo & A Lafuente

  4. Clinic Schizophrenia program, Psychiatry service, Hospital Clínic de Barcelona, Barcelona, Spain

    E Parellada & M Bernardo

  5. Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

    M Bernardo

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Correspondence to A Lafuente.

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Mas, S., Gassó, P., Parellada, E. et al. Network analysis of gene expression in peripheral blood identifies mTOR and NF-κB pathways involved in antipsychotic-induced extrapyramidal symptoms. Pharmacogenomics J 15, 452–460 (2015). https://doi.org/10.1038/tpj.2014.84

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