title: FKBP5 genotype-dependent DNA methylation and mRNA regulation after psychosocial stress in remitted depression and healthy controls.
abstract: BACKGROUND
  Polymorphisms in the FK506 binding protein 5 (FKBP5) gene have been shown to influence glucocorticoid receptor sensitivity, stress response regulation, and depression risk in traumatized subjects, with most consistent findings reported for the functional variant rs1360780. In the present study, we investigated whether the FKBP5 polymorphism rs1360780 and lifetime history of major depression are associated with DNA methylation and FKBP5 gene expression after psychosocial stress.
  
  
  METHODS
  A total of 116 individuals with a positive (n = 61) and negative (n = 55) lifetime history of major depression participated in the Trier Social Stress Test. We assessed plasma cortisol concentrations, FKBP5 mRNA expression, and CpG methylation of FKBP5 intron 7 in peripheral blood cells.
  
  
  RESULTS
  Genotype-dependent plasma cortisol response to psychosocial stress exposure was observed in healthy controls, with the highest and longest-lasting cortisol increase in subjects with the TT genotype of the FKBP5 polymorphism rs1360780, and healthy controls carrying the T risk allele responded with a blunted FKBP5 mRNA expression after psychosocial stress. No genotype effects could be found in remitted depression.
  
  
  CONCLUSIONS
  The FKBP5 rs1360780 polymorphism is associated with plasma cortisol and FKBP5 mRNA expression after psychosocial stress in healthy controls but not in remitted depression. Preliminary results of the DNA methylation analysis suggest that epigenetic modifications could be involved.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Nina
authors.initials: N
authors.lastname: Höhne
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Maximilian
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Franziska
authors.initials: F
authors.lastname: Merz
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Hildegard
authors.initials: H
authors.lastname: Pfister
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Tanja
authors.initials: T
authors.lastname: Brückl
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Petra
authors.initials: P
authors.lastname: Zimmermann
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer).
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany (Dr Höhne, Poidinger, Merz, Dipl-Inf Pfister, Drs Brückl, Zimmermann, Uhr, Holsboer, and Ising); HMNC GmbH, Munich, Germany (Dr Holsboer). ising@mpipsykl.mpg.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007438:Introns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood; D012938:Social Perception; D013315:Stress, Psychological / Q000097:blood* / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000097:blood* / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: DNA methylation; FKBP5; HPA axis; gene expression; major depression