title: DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy.
abstract: BACKGROUND
  Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases.
  
  
  METHODS
  The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR(⁎)D genome-wide dataset (n=1892) for replication.
  
  
  RESULTS
  Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR(⁎)D a cluster of SNPs from 20 to 40Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325bp from rs778294).
  
  
  CONCLUSIONS
  Relatively small size of the original sample and focus on only three candidate genes.
  
  
  CONCLUSIONS
  The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy.
authors.affiliation: Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Arias
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. Electronic address: alessandro.serretti@unibo.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Drago
authors.affiliation: Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Mitjans
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Centre de Salut Mental Esquerre de l´Eixample, Hospital Clínic i Provincial de Barcelona. Institut d'Investigació Biomèdica Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Gastó
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Centre de Salut Mental Esquerre de l´Eixample, Hospital Clínic i Provincial de Barcelona. Institut d'Investigació Biomèdica Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Catalán
authors.affiliation: Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013030:Spain; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation
keywords: Antidepressant; DAOA; DISC1; Gene; Major depression; TSNAX