title: The FKBP5 polymorphism rs1360780 influences the effect of an algorithm-based antidepressant treatment and is associated with remission in patients with major depression.
abstract: OBJECTIVE
  The FKBP5-gene influences the HPA-system by modulating the sensitivity of the glucocorticoid receptor (GR). The polymorphism rs1360780 has been associated with response in studies with heterogeneous antidepressant treatment. In contrast, several antidepressant studies with standardized antidepressant treatment could not detect this effect. We therefore compared patients with standardized vs naturalistic antidepressant treatment to (a) investigate a possible interaction between FKBP5-genotype and treatment mode and (b) replicate the effect of the FKBP5-genotype on antidepressant treatment outcome.
  
  
  METHODS
  A total of 298 major depressive disorder (MDD) inpatients from the multicentred German project and the Zurich Algorithm Project were genotyped for their FKBP5 status. Patients were treated as usual (n=127) or according to a standardized algorithm (n=171). Main outcome criteria was remission (Hamilton Depression Rating Scale-21<10).
  
  
  RESULTS
  We detected an interaction of treatment as usual (TAU) treatment and C-allele with the worst outcome for patients combining those two factors (HR=0.46; p=0.000). Even though C-allele patients did better when treated in the structured, stepwise treatment algorithm (SSTR) group, we still could confirm the influence of the FKBP5-genotype in the whole sample (HR=0.52; p=0.01).
  
  
  CONCLUSIONS
  This is the first study to show an interaction between a genetic polymorphism and treatment mode. Patients with the C-allele of the rs1360780 polymorphism seem to benefit from a standardized antidepressant treatment.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany thomas.stamm@charite.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Stamm
authors.affiliation: Max Planck Institute for Psychiatry, München, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Rampp
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Wiethoff
authors.affiliation: Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Stingl
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.affiliation: School of Psychology, University College Dublin, Dublin, Ireland.
authors.forename: Grace
authors.initials: G
authors.lastname: O Malley
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Ricken
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Ludwig-Maximilian University, München, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Seemüller
authors.affiliation: Max Planck Institute for Psychiatry, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Keck
authors.affiliation: City and Hackney Centre for Mental Health, East London NHS Foundation Trust, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Fisher
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gaebel
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Ludwig-Maximilian University, München, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Mazda
authors.initials: M
authors.lastname: Adli
mesh_terms: D000328:Adult; D000465:Algorithms; D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D016896:Treatment Outcome; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000928:Antidepressive Agents; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Depression; algorithm; pharmacogenetics