FKBP5 haplotypes and PTSD modulate the resting-state brain activity in Han Chinese adults who lost their only child

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 r...

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Published in:	Translational psychiatry 2020-03, Vol.10 (1), p.91-91, Article 91
Main Authors:	Qi, Rongfeng, Luo, Yifeng, Zhang, Li, Weng, Yifei, Surento, Wesley, Jahanshad, Neda, Xu, Qiang, Yin, Yan, Li, Lingjiang, Cao, Zhihong, Thompson, Paul M, Lu, Guang Ming
Format:	Article
Language:	eng
Subjects:	Adult Brain - metabolism Child China Haplotypes Humans Only Child Polymorphism, Single Nucleotide Post traumatic stress disorder Stress Disorders, Post-Traumatic - genetics Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism
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Summary:	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.
ISSN:	2158-3188 2158-3188