dc.creator | Lago, Santiago G. | es |
dc.creator | Tomasik, Jakub | es |
dc.creator | Van Rees, Geertje F. | es |
dc.creator | Rustogi, Nitin | es |
dc.creator | Vázquez-Bourgon, Javier | es |
dc.creator | Papiol, Sergi | es |
dc.creator | Suarez-Pinilla, Paula | es |
dc.creator | Crespo Facorro, Benedicto | es |
dc.creator | Bahn, Sabine | es |
dc.date.accessioned | 2022-11-04T14:10:00Z | |
dc.date.available | 2022-11-04T14:10:00Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Lago, S.G., Tomasik, J., Van Rees, G.F., Rustogi, N., Vázquez-Bourgon, J., Papiol, S.,...,Bahn, S. (2022). Peripheral lymphocyte signaling pathway deficiencies predict treatment response in first-onset drug-naïve schizophrenia. BRAIN BEHAVIOR AND IMMUNITY, 103, 37-49. https://doi.org/10.1016/j.bbi.2022.03.016. | |
dc.identifier.issn | 0889-1591 | es |
dc.identifier.issn | 1090-2139 | es |
dc.identifier.uri | https://hdl.handle.net/11441/138983 | |
dc.description.abstract | Despite being a major cause of disability worldwide, the pathophysiology of schizophrenia and molecular basis of
treatment response heterogeneity continue to be unresolved. Recent evidence suggests that multiple aspects of
pathophysiology, including genetic risk factors, converge on key cell signaling pathways and that exploration of
peripheral blood cells might represent a practical window into cell signaling alterations in the disease state. We
employed multiplexed phospho-specific flow cytometry to examine cell signaling epitope expression in periph eral blood mononuclear cell (PBMC) subtypes in drug-naïve schizophrenia patients (n = 49) relative to controls
(n = 61) and relate these changes to serum immune response proteins, schizophrenia polygenic risk scores and
clinical effects of treatment, including drug response and side effects, over the longitudinal course of antipsy chotic treatment. This revealed both previously characterized (Akt1) and novel cell signaling epitopes (IRF-7
(pS477/pS479), CrkL (pY207), Stat3 (pS727), Stat3 (pY705) and Stat5 (pY694)) across PBMC subtypes which
were associated with schizophrenia at disease onset, and correlated with type I interferon-related serum mole cules CD40 and CXCL11. Alterations in Akt1 and IRF-7 (pS477/pS479) were additionally associated with
polygenic risk of schizophrenia. Finally, changes in Akt1, IRF-7 (pS477/pS479) and Stat3 (pS727) predicted
development of metabolic and cardiovascular side effects following antipsychotic treatment, while IRF-7
(pS477/pS479) and Stat3 (pS727) predicted early improvements in general psychopathology scores measured
using the Brief Psychiatric Rating Scale (BPRS). These findings suggest that peripheral blood cells can provide an
accessible surrogate model for intracellular signaling alterations in schizophrenia and have the potential to
stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic and
cardiovascular side effects following antipsychotic therapy. | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | es |
dc.relation.ispartof | BRAIN BEHAVIOR AND IMMUNITY, 103, 37-49. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Schizophrenia | es |
dc.subject | Lymphocyte | es |
dc.subject | Signaling pathway | es |
dc.subject | Interferon | es |
dc.subject | Polygenic risk score | es |
dc.subject | Treatment response | es |
dc.title | Peripheral lymphocyte signaling pathway deficiencies predict treatment response in first-onset drug-naïve schizophrenia | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Psiquiatría | es |
dc.relation.publisherversion | https://bibliometria.us.es/prisma/publicacion/202532 | es |
dc.identifier.doi | 10.1016/j.bbi.2022.03.016 | es |
dc.contributor.group | Universidad de Sevilla. CTS1086 : Psiquiatría Traslacional. | es |
dc.journaltitle | BRAIN BEHAVIOR AND IMMUNITY | es |
dc.publication.volumen | 103 | es |
dc.publication.initialPage | 37 | es |
dc.publication.endPage | 49 | es |