title: DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice.
abstract: BACKGROUND
  Impulsivity in intertemporal choice has been operationalized as "delay discounting", referring to the preference for a sooner, smaller reward. FK506 binding protein 5 (FKBP5) is a co-chaperone of the glucocorticoid receptor (GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma cortisol levels. High cortisol levels are associated with low impulsivity in intertemporal choice. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in FKBP5 on delay discounting.
  
  
  METHODS
  The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed Kirby's monetary choice questionnaire (MCQ) and donated a whole blood sample. Five SNPs in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k).
  
  
  RESULTS
  Two SNPs were excluded from analysis because of their low minor allelic frequencies. The SNP rs1360780 showed a significant association; participants with more minor alleles (T) were less impulsive in intertemporal choice for delayed gain (multiplicity-corrected P = 0.047).
  
  
  CONCLUSIONS
  The significant SNP rs1360780 is located in the region adjacent to the hormone response element (HRE)-binding sequence where transcription factors bind and alter the transcription of FKBP5. A minor allele (T) of rs1360780, which causes FKBP5 overexpression, may reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR resistance and the subsequent high cortisol levels. This is the first study to demonstrate an association between FKBP5 and impulsivity in intertemporal choice.
authors.affiliation: Department of Psychiatry, Sakae Seijinkai Hospital, Kanagawa, Japan. yoshiya-tky@umin.ac.jp
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Taiki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Ko
authors.initials: K
authors.lastname: Ukawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Akane
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shimada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Umekage
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasak
mesh_terms: D000328:Adult; D002755:Choice Behavior / Q000502:physiology*; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007175:Impulsive Behavior / Q000235:genetics*; D007564:Japan; D016014:Linear Models; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012201:Reward; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D011795:Surveys and Questionnaires; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D013997:Time Factors; D000099159:Tacrolimus Binding Protein 5
chemical_list: D004247:DNA; D006854:Hydrocortisone; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: FK506 binding protein 5; impulsivity; molecular neuroeconomics; single nucleotide polymorphism; time-discount rate