Bryant R A, Felmingham K L, Liddell B, Das P, Malhi G S
School of Psychology, University of New South Wales, Sydney, NSW, Australia.
Department of Psychiatry, University of Sydney, Sydney, NSW, Australia.
Transl Psychiatry. 2016 Oct 18;6(10):e925. doi: 10.1038/tp.2016.149.
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles. Spatial maps, power spectra and connectivity in neural networks active during resting state were assessed with functional magnetic resonance imaging (fMRI). During resting-state fMRI, FKBP5 low-risk allele group displayed more power in the low frequency range (<0.1 Hz) than the high-risk allele group, who had significantly more power in higher frequency bins (>0.15 Hz). This difference was apparent only in a frontotemporoparietal network underpinning salience detection and emotion processing. This study provides initial evidence that the risk alleles of the FKBP5 polymorphism are associated with different resting-state activity in a frontotemporal-parietal network, and may point to mechanisms underpinning high-risk carriers' vulnerability to severe stress reactions.
FKBP5基因多态性是糖皮质激素系统的关键调节因子，支撑着应激反应，且风险等位基因会增加患创伤后应激障碍的易感性。为了阐明不受精神病理学混杂因素影响的FKBP5风险等位基因的具体作用，本研究调查了FKBP5基因多态性的高风险等位基因在静息状态下是否具有独特的神经活动特征。基于FKBP5基因区域的四个单核苷酸多态性（rs3800373、rs9296158、rs1360780和rs9470080）选择了37名健康参与者，以确定FKBP5高风险和低风险等位基因的携带者。使用功能磁共振成像（fMRI）评估静息状态下活跃神经网络中的空间图谱、功率谱和连通性。在静息态fMRI期间，FKBP5低风险等位基因组在低频范围（<0.1Hz）显示出比高风险等位基因组更多的功率，而高风险等位基因组在较高频率区间（>0.15Hz）具有显著更多的功率。这种差异仅在一个支持显著性检测和情绪处理的额颞顶网络中明显。本研究提供了初步证据，表明FKBP5基因多态性的风险等位基因与额颞顶网络中不同的静息态活动相关，并可能指向高风险携带者易患严重应激反应的潜在机制。
