Department of Psychiatry, Sakae Seijinkai Hospital, Kanagawa, Japan.
Asia Pac Psychiatry. 2013 Mar;5(1):31-8. doi: 10.1111/appy.12009.
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.
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).
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).
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.
在跨期选择中的冲动性已被操作化为“延迟折扣”，指的是对更短、更小的奖励的偏好。FK506 结合蛋白 5（FKBP5）是糖皮质激素受体（GR）的共伴侣。FKBP5 过表达导致 GR 抵抗，导致血浆皮质醇水平升高。高皮质醇水平与跨期选择中的低冲动性有关。本研究旨在探讨 FKBP5 中的单核苷酸多态性（SNP）对延迟折扣的影响。
参与者包括 91 名健康的日本成年人（66 名男性和 25 名女性，平均年龄为 40.9±6.9 岁）。每位参与者完成 Kirby 的货币选择问卷（MCQ）并捐献全血样本。使用 DigiTag2 对 FKBP5 中的 5 个 SNP 进行基因分型。对双曲线时间折扣率（k）进行了 100,000 次置换的 SNP 线性回归分析。
由于其低次要等位基因频率，有两个 SNP 被排除在分析之外。SNP rs1360780 显示出显著的相关性；具有更多次要等位基因（T）的个体在延迟获得的跨期选择中表现出较低的冲动性（多重校正 P=0.047）。
显著的 SNP rs1360780 位于与激素反应元件（HRE）结合序列相邻的区域，转录因子在该区域结合并改变 FKBP5 的转录。rs1360780 的次要等位基因（T），导致 FKBP5 过表达，可能通过 GR 抵抗和随后的高皮质醇水平降低跨期选择中的冲动性（即延迟折扣）。这是第一个证明 FKBP5 与跨期选择中的冲动性之间存在关联的研究。
