FAS -670A>G genetic polymorphism Is associated with treatment resistant depression
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.22/18918 |
Resumo: | Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875–20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362–87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072–13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. Small sample size. Patients used antidepressants with different mechanisms of action. To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity. |
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FAS -670A>G genetic polymorphism Is associated with treatment resistant depressionNeurogenesisNeuroplasticityFASAntidepressantsTreatment resistant depressionPolymorphismsHippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875–20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362–87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072–13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. Small sample size. Patients used antidepressants with different mechanisms of action. To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity.ElsevierRepositório Científico do Instituto Politécnico do PortoSantos, MarleneCarvalho, SerafimLima, LuísMota-Pereira, JorgePimentel, PauloMaia, DulceCorreia, DianaGomes, SofiaCruz, AgostinhoMedeiros, Rui2021-11-22T12:21:12Z2015-10-012015-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/18918engSantos, M., Carvalho, S., Lima, L., Mota-Pereira, J., Pimentel, P., Maia, D., Correia, D., Gomes, S., Cruz, A., & Medeiros, R. (2015). FAS -670A>G genetic polymorphism Is associated with Treatment Resistant Depression. Journal of Affective Disorders, 185, 164-169. https://doi.org/https://doi.org/10.1016/j.jad.2015.06.0270165-032710.1016/j.jad.2015.06.027info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-13T13:12:10Zoai:recipp.ipp.pt:10400.22/18918Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:38:57.999519Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
title |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
spellingShingle |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression Santos, Marlene Neurogenesis Neuroplasticity FAS Antidepressants Treatment resistant depression Polymorphisms |
title_short |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
title_full |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
title_fullStr |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
title_full_unstemmed |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
title_sort |
FAS -670A>G genetic polymorphism Is associated with treatment resistant depression |
author |
Santos, Marlene |
author_facet |
Santos, Marlene Carvalho, Serafim Lima, Luís Mota-Pereira, Jorge Pimentel, Paulo Maia, Dulce Correia, Diana Gomes, Sofia Cruz, Agostinho Medeiros, Rui |
author_role |
author |
author2 |
Carvalho, Serafim Lima, Luís Mota-Pereira, Jorge Pimentel, Paulo Maia, Dulce Correia, Diana Gomes, Sofia Cruz, Agostinho Medeiros, Rui |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Santos, Marlene Carvalho, Serafim Lima, Luís Mota-Pereira, Jorge Pimentel, Paulo Maia, Dulce Correia, Diana Gomes, Sofia Cruz, Agostinho Medeiros, Rui |
dc.subject.por.fl_str_mv |
Neurogenesis Neuroplasticity FAS Antidepressants Treatment resistant depression Polymorphisms |
topic |
Neurogenesis Neuroplasticity FAS Antidepressants Treatment resistant depression Polymorphisms |
description |
Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875–20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362–87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072–13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. Small sample size. Patients used antidepressants with different mechanisms of action. To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-01 2015-10-01T00:00:00Z 2021-11-22T12:21:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.22/18918 |
url |
http://hdl.handle.net/10400.22/18918 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Santos, M., Carvalho, S., Lima, L., Mota-Pereira, J., Pimentel, P., Maia, D., Correia, D., Gomes, S., Cruz, A., & Medeiros, R. (2015). FAS -670A>G genetic polymorphism Is associated with Treatment Resistant Depression. Journal of Affective Disorders, 185, 164-169. https://doi.org/https://doi.org/10.1016/j.jad.2015.06.027 0165-0327 10.1016/j.jad.2015.06.027 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799131477932244992 |