title: DNA sequence variants of the FKBP5 gene are associated with unipolar depression.
abstract: FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression. Previously, three studies identified single nucleotide polymorphisms (SNPs) in the FKBP5 gene associated with response to antidepressants, and one study found an association with diagnosis of depression. We selected five markers from the region of interest. A case-control sample comprising 268 German in-patients with recurrent unipolar depression, and 284 German controls recruited from the general population were available. Association of the selected FKBP5 sequence variants with clinical depression were analysed. In addition, we explored association with treatment response by (a) the Hamilton Depression Rating Scale and (b) the dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test, as well as association with hippocampal volumes in a subpopulation of 110 patients. For three of the five investigated SNPs we were able to show association with the diagnosis of depression. In the subpopulation of 110 patients, diagnosis-related alleles were also associated with the reduction of cortisol secretion in the Dex/CRH test during a 4-wk treatment period, while psychopathological changes were not associated. Furthermore, diagnosis-related alleles were associated with reduction of the hippocampal volume. This study extends the replicated association of a promoter SNP with antidepressant response on a biological level by demonstrating normalization of the cortisol response under Dex/CRH stimulation during treatment. Furthermore, several of the investigated SNPs were associated with the disease status and the intermediate phenotype of hippocampal volume.
authors.affiliation: Department of Psychiatry, University of Bonn, Germany. astrid.zobel@ukb.uni-bonn.de
authors.forename: Astrid
authors.initials: A
authors.lastname: Zobel
authors.forename: Anna
authors.initials: A
authors.lastname: Schuhmacher
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Susanne
authors.initials: S
authors.lastname: Höfels
authors.forename: Olrik
authors.initials: O
authors.lastname: von Widdern
authors.forename: Martin
authors.initials: M
authors.lastname: Metten
authors.forename: Ute
authors.initials: U
authors.lastname: Pfeiffer
authors.forename: Claudia
authors.initials: C
authors.lastname: Hanses
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Lukas
authors.initials: L
authors.lastname: Scheef
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Block
authors.forename: Hans H
authors.initials: HH
authors.lastname: Schild
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Sibylle G
authors.initials: SG
authors.lastname: Schwab
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence / Q000235:genetics*; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D015283:Citalopram; D005819:Genetic Markers; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5