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FKBP5 haplotypes and PTSD modulate the resting-state brain activity in Han Chinese adults who lost their only child.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2020-03-13 , DOI: 10.1038/s41398-020-0770-5
Rongfeng Qi 1, 2 , Yifeng Luo 3 , Li Zhang 4 , Yifei Weng 1 , Wesley Surento 2 , Neda Jahanshad 2 , Qiang Xu 1 , Yan Yin 5 , Lingjiang Li 4 , Zhihong Cao 3 , Paul M Thompson 2 , Guang Ming Lu 1
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The stress-related gene FKBP5 has been related to dysregulated glucocorticoid receptor (GR) signaling, showing increased GR sensitivity in trauma-exposed subjects with post-traumatic stress disorder (PTSD) but not in those without PTSD. However, the neural mechanism underlying the effects of FKBP5 remains poorly understood. Two hundred and thirty-seven Han Chinese adults who had lost their only child were included. Four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. All 179 participants were successfully divided into three FKBP5 diplotype subgroups according to two major FKBP5 H1 and H2 yin yang haplotypes. Brain average spectral power was compared using a two-way (PTSD diagnosis and FKBP5 diplotypes) analysis of covariance within four separate frequency bands (slow-5, slow-4, slow-3, and slow-2). Adults with PTSD showed lower spectral power in bilateral parietal lobules in slow-4 and in left inferior frontal gyrus (IFG) in slow-5. There was significant FKBP5 diplotype main effect in anterior cingulate cortex (ACC) in slow-4 (H1/H1 higher than other two subgroups), and in precentral/postcentral gyri and middle cingulate cortex (MCC) in slow-3 (H2/H2 higher than other two subgroups). Also, there was a significant diagnosis × FKBP5 diplotype interaction effect in right parietal lobule in slow-3. These findings suggest that adults with PTSD have lower low-frequency power in executive control network regions. Lower power in ACC and greater power in the motor/sensory areas in FKBP5 high-risk diplotype group suggest a disturbance of emotional processing and hypervigilance/sensitization to threatening stimuli. The interaction effect of diagnosis × FKBP5 in parietal lobule may contribute to PTSD development.



中文翻译:

FKBP5 单倍型和 PTSD 调节失去独生子女的汉族成年人的静息状态大脑活动。

压力相关基因FKBP5与糖皮质激素受体 (GR) 信号传导失调有关,在患有创伤后应激障碍 (PTSD) 的创伤暴露受试者中显示出 GR 敏感性增加,但在没有 PTSD 的受试者中则没有。然而, FKBP5影响的神经机制仍然知之甚少。237 名失去独生子女的汉族成年人也包括在内。对四个FKBP5单核苷酸多态性(rs3800373、rs9296158、rs1360780 和 rs9470080)进行了基因分型。根据两个主要的FKBP5 ,所有 179 名参与者成功分为三个FKBP5双倍型亚组H1 和 H2 阴阳单倍型。脑平均光谱功率使用双向(PTSD 诊断和FKBP5双倍型)分析四个独立频带(慢 5、慢 4、慢 3 和慢 2)内的协方差进行比较。患有 PTSD 的成年人在 slow-4 中的双侧顶叶和在 slow-5 中的左侧额下回 (IFG) 中显示出较低的光谱功率。前扣带回皮层(ACC)在slow -4(H1/H1高于其他两个亚组)和中前/中央后回和中扣带皮层(MCC)在slow-3(H2/H2高于其他两个子组)。此外,有一个显着的诊断 × FKBP5slow-3 右顶叶双倍型相互作用效应。这些研究结果表明,患有 PTSD 的成年人在执行控制网络区域的低频功率较低。在FKBP5高风险双倍型组中,ACC 的较低功率和运动/感觉区域的较大功率表明情绪处理和过度警觉/对威胁刺激敏感的障碍。诊断与顶叶FKBP5的交互作用可能有助于 PTSD 的发展。

更新日期:2020-03-13
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