Dataset for: FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory

FK506 binding protein 51(FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder, and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373, and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes.

FK506结合蛋白51（FK506 binding protein 51, FKBP5）是热休克蛋白90的辅助伴侣蛋白，可显著影响糖皮质激素受体的敏感性。FKBP5基因的单核苷酸多态性（single nucleotide polymorphisms, SNPs）与下丘脑-垂体-肾上腺（hypothalamus-pituitary-adrenal, HPA）轴功能异常、多个认知脑区的结构与功能改变，以及创伤后应激障碍、重度抑郁症、双相情感障碍和自杀行为的易感性升高密切相关。目前此类关联的潜在机制尚不完全明晰，但有研究推测，此类SNPs对情绪记忆系统的影响可能是其中的关键环节。本研究共纳入112名受试者，在学习由42个单词组成的列表前，分别令其接受社会评价冷水加压试验（应激条件）或对照处理（无应激条件）。受试者分别在学习结束后即刻（即时自由回忆）以及24小时后（自由回忆与再认）接受记忆能力评估。同时，受试者提供了唾液样本，用于对3个FKBP5基因多态性位点——rs1360780、rs3800373及rs9296158——进行基因分型。研究结果显示，应激可损伤风险等位基因携带者的即时回忆能力。更为重要的是，应激可提升非风险等位基因携带者的长期回忆与再认记忆能力，而此类效应在风险等位基因携带者中完全缺失。后续分析表明，非风险等位基因携带者的记忆表现与唾液皮质醇水平呈显著正相关，而风险等位基因携带者中未观察到此关联。上述研究结果提示，FKBP5风险等位基因携带者可能存在应激反应系统敏化的表型，尤其是针对应激诱导的皮质醇水平变化，本研究结果或有助于阐明FKBP5基因的SNPs如何增加应激相关精神障碍及其相关表型的发病风险。