Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis
Authors
Andronis, Christos
Silva, João
Lekka, Eftychia
Virvilis, Vassilis
Carmo, Helena
Bampali, Konstantina
Ernst, Margot

Hu, Yang
Loryan, Irena
Richard, Jacques
Carvalho, Félix
Savić, Miroslav

Article (Published version)
Metadata
Show full item recordAbstract
Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCA...Es. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.
Keywords:
Adverse outcome pathways / Cross-talk analysis / Neurotoxicity / Pharmaceuticals’ safety / Psychiatric/psychological adverse eventsSource:
Archives of Toxicology, 2020, 94, 8, 2829-2845Publisher:
- Springer Nature Switzerland
Funding / projects:
DOI: 10.1007/s00204-020-02788-1
ISSN: 0340-5761
WoS: 000538490000001
Scopus: 2-s2.0-85086100612
Collections
Institution/Community
PharmacyTY - JOUR AU - Andronis, Christos AU - Silva, João AU - Lekka, Eftychia AU - Virvilis, Vassilis AU - Carmo, Helena AU - Bampali, Konstantina AU - Ernst, Margot AU - Hu, Yang AU - Loryan, Irena AU - Richard, Jacques AU - Carvalho, Félix AU - Savić, Miroslav PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3613 AB - Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage. PB - Springer Nature Switzerland T2 - Archives of Toxicology T1 - Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis VL - 94 IS - 8 SP - 2829 EP - 2845 DO - 10.1007/s00204-020-02788-1 ER -
@article{ author = "Andronis, Christos and Silva, João and Lekka, Eftychia and Virvilis, Vassilis and Carmo, Helena and Bampali, Konstantina and Ernst, Margot and Hu, Yang and Loryan, Irena and Richard, Jacques and Carvalho, Félix and Savić, Miroslav", year = "2020", abstract = "Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.", publisher = "Springer Nature Switzerland", journal = "Archives of Toxicology", title = "Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis", volume = "94", number = "8", pages = "2829-2845", doi = "10.1007/s00204-020-02788-1" }
Andronis, C., Silva, J., Lekka, E., Virvilis, V., Carmo, H., Bampali, K., Ernst, M., Hu, Y., Loryan, I., Richard, J., Carvalho, F.,& Savić, M.. (2020). Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis. in Archives of Toxicology Springer Nature Switzerland., 94(8), 2829-2845. https://doi.org/10.1007/s00204-020-02788-1
Andronis C, Silva J, Lekka E, Virvilis V, Carmo H, Bampali K, Ernst M, Hu Y, Loryan I, Richard J, Carvalho F, Savić M. Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis. in Archives of Toxicology. 2020;94(8):2829-2845. doi:10.1007/s00204-020-02788-1 .
Andronis, Christos, Silva, João, Lekka, Eftychia, Virvilis, Vassilis, Carmo, Helena, Bampali, Konstantina, Ernst, Margot, Hu, Yang, Loryan, Irena, Richard, Jacques, Carvalho, Félix, Savić, Miroslav, "Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis" in Archives of Toxicology, 94, no. 8 (2020):2829-2845, https://doi.org/10.1007/s00204-020-02788-1 . .