Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach

Neuropharmacology
Gaël QesseveurBruno P Guiard

Abstract

Pharmacological studies have yielded valuable insights into the role of the serotonin 2A (5-HT2A) receptor in major depressive disorder (MDD) and antidepressant drugs (ADs) response. However, it is still unknown whether genetic variants in the HTR2A gene affect the therapeutic outcome of ADs and the mechanism underlying the regulation of such response remains poorly described. In this context, a translational human-mouse study offers a unique opportunity to address the possibility that variations in the HTR2A gene may represent a relevant marker to predict the efficacy of ADs. In a first part of this study, we investigated in depressed patients the effect of three HTR2A single nucleotide polymorphisms (SNPs), selected for their potential functional consequences on 5-HT2A receptor (rs6313, rs6314 and rs7333412), on response and remission rates after 3 months of antidepressant treatments. We also explored the consequences of the constitutive genetic inactivation of the 5-HT2A receptor (i.e. in 5-HT2A(-/-) mice) on the activity of acute and prolonged administration of SSRIs. Our clinical data indicate that GG patients for the rs7333412 SNP were less prone to respond to ADs than AA/AG patients. In the preclinical study, we demonstr...Continue Reading

References

Aug 1, 1982·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G K Aghajanian, C P Vandermaelen
Aug 8, 2001·The European Journal of Neuroscience·S Haj-Dahmane
Mar 26, 2003·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Pierre Blier
Feb 12, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mounira BanasrAnnie Daszuta
Sep 28, 2004·The International Journal of Neuropsychopharmacology·Sylvie LemondePaul R Albert
Feb 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mikko SairanenEero Castrén
May 12, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gerard J MarekFrancesc Artigas
Apr 28, 2006·American Journal of Human Genetics·Francis J McMahonHusseini Manji
Aug 3, 2007·The American Journal of Psychiatry·Diane WardenA John Rush
Sep 18, 2009·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Susanne LucaeKatharina Domschke
Nov 20, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sonja HorstmannElisabeth B Binder
Nov 26, 2009·Neuromolecular Medicine·Taro KishiNakao Iwata
Jan 6, 2010·The International Journal of Neuropsychopharmacology·Gonzalo LajeFrancis J McMahon
Feb 16, 2010·Neuron·Jesse W Richardson-JonesE David Leonardo
Feb 16, 2010·Neuropharmacology·Magdalena ZaniewskaMałgorzata Filip
Apr 9, 2010·The International Journal of Neuropsychopharmacology·Pablo Vázquez-BorsettiFrancesc Artigas
May 11, 2010·International Clinical Psychopharmacology·Magali NoroIsabelle Massat
Nov 8, 2011·Brain Research Bulletin·Shu HasegawaMirko Diksic
Nov 23, 2011·The European Journal of Neuroscience·Vera Kiyasova, Patricia Gaspar
Jun 5, 2013·Progress in Neuro-psychopharmacology & Biological Psychiatry·Tomihisa NiitsuAlessandro Serretti

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Citations

Jun 17, 2016·Expert Opinion on Drug Metabolism & Toxicology·Chiara FabbriAlessandro Serretti
Feb 13, 2020·Frontiers in Psychiatry·Dan XiangZhongchun Liu
Sep 1, 2017·Journal of Psychopharmacology·R L Carhart-Harris, D J Nutt
Dec 28, 2019·Pharmaceutics·Stefano FortinguerraAlessandro Buriani
Aug 30, 2017·Frontiers in Molecular Neuroscience·Mylène HervéEl Chérif Ibrahim

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