Association of FKBP5 polymorphisms and resting-state activity in a frontotemporal-parietal network.
Association of FKBP5 polymorphisms and resting-state activity in a frontotemporal-parietal network.
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DOI：
10.1038/tp.2016.149
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发表时间：
2016-10-18
影响因子：
6.8
通讯作者：
Malhi GS
中科院分区：
文献类型：
--
作者：
Bryant RA;Felmingham KL;Liddell B;Das P;Malhi GS
FKBP5多态性是支持应激反应的糖皮质激素系统的关键调节因子，风险等位基因可以增加患创伤后应激障碍的易感性。为了描述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多态性的高风险等位基因是否以静息状态下独特的神经活动为特征。根据FKBP5基因区域的4个snp （rs3800373、rs9296158、rs1360780和rs9470080）选择37名健康参与者，确定FKBP5高、低风险等位基因携带者。利用功能磁共振成像（fMRI）对静息状态下活动神经网络的空间图、功率谱和连通性进行评估。在静息状态fMRI中，FKBP5低风险等位基因组在低频范围（<0.1 Hz）比高风险等位基因组表现出更大的功率，后者在高频范围（>0.15 Hz）具有更大的功率。这种差异只在支撑显著性检测和情绪处理的额颞顶叶网络中表现明显。该研究提供了FKBP5多态性的风险等位基因与额颞顶网络中不同静息状态活动相关的初步证据，并可能指出高危携带者易受严重应激反应的机制。
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.