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Neuroplasticity and second messenger pathways in antidepressant efficacy: pharmacogenetic results from a prospective trial investigating treatment resistance.
Fabbri, Chiara; Crisafulli, Concetta; Calati, Raffaella; Albani, Diego; Forloni, Gianluigi; Calabrò, Marco; Martines, Rosalba; Kasper, Siegfried; Zohar, Joseph; Juven-Wetzler, Alzbeta; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Serretti, Alessandro.
Afiliação
  • Fabbri C; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.
  • Crisafulli C; Department of Biomedical Science, Odontoiatric and Morphological and Functional Images, University of Messina, Messina, Italy.
  • Calati R; INSERM U1061, France and FondaMental Foundation, University of Montpellier UM1, Montpellier, France.
  • Albani D; Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
  • Forloni G; Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
  • Calabrò M; Department of Biomedical Science, Odontoiatric and Morphological and Functional Images, University of Messina, Messina, Italy.
  • Martines R; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.
  • Kasper S; Laboratory of Biology of Neurodegenerative Disorders, Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
  • Zohar J; Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
  • Juven-Wetzler A; Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Souery D; Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Montgomery S; Laboratoire de Psychologie Medicale, Centre Européen de Psychologie Medicale, Universitè Libre de Bruxelles and Psy Pluriel, Brussels, Belgium.
  • Mendlewicz J; lmperial College School of Medicine, London, UK.
  • Serretti A; Université Libre de Bruxelles, Brussels, Belgium.
Eur Arch Psychiatry Clin Neurosci ; 267(8): 723-735, 2017 Dec.
Article em En | MEDLINE | ID: mdl-28260126
Genes belonging to neuroplasticity, monoamine, circadian rhythm, and transcription factor pathways were investigated as modulators of antidepressant efficacy. The present study aimed (1) to replicate previous findings in an independent sample with treatment-resistant depression (TRD), and (2) to perform a pathway analysis to investigate the possible molecular mechanisms involved. 220 patients with major depressive disorder who were non-responders to a previous antidepressant were treated with venlafaxine for 4-6 weeks and in case of non-response with escitalopram for 4-6 weeks. Symptoms were assessed using the Montgomery Asberg Depression Rating Scale. The phenotypes were response and remission to venlafaxine, non-response (TRDA) and non-remission (TRDB) to neither venlafaxine nor escitalopram. 50 tag SNPs in 14 genes belonging to the pathways of interest were tested for association with phenotypes. Molecular pathways (KEGG database) that included one or more of the genes associated with the phenotypes were investigated also in the STAR*D sample. The associations between ZNF804A rs7603001 and response, CREB1 rs2254137 and remission were replicated, as well as CHL1 rs2133402 and lower risk of TRD. Other CHL1 SNPs were potential predictors of TRD (rs1516340, rs2272522, rs1516338, rs2133402). The MAPK1 rs6928 SNP was consistently associated with all the phenotypes. The protein processing in endoplasmic reticulum pathway (hsa04141) was the best pathway that may explain the mechanisms of MAPK1 involvement in antidepressant response. Signals in genes previously associated with antidepressant efficacy were confirmed for CREB1, ZNF804A and CHL1. These genes play pivotal roles in synaptic plasticity, neural activity and connectivity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farmacogenética / Citalopram / Sistemas do Segundo Mensageiro / Antidepressivos de Segunda Geração / Transtorno Depressivo Maior / Transtorno Depressivo Resistente a Tratamento / Cloridrato de Venlafaxina / Plasticidade Neuronal Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farmacogenética / Citalopram / Sistemas do Segundo Mensageiro / Antidepressivos de Segunda Geração / Transtorno Depressivo Maior / Transtorno Depressivo Resistente a Tratamento / Cloridrato de Venlafaxina / Plasticidade Neuronal Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article