Reduced Peripheral Expression of the Glucocorticoid Receptor α Isoform in Individuals with Posttraumatic Stress Disorder: A Cumulative Effect of Trauma Burden
Reduced Peripheral Expression of the Glucocorticoid Receptor α Isoform in Individuals with Posttraumatic Stress Disorder: A Cumulative Effect of Trauma Burden
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DOI：
10.1371/journal.pone.0086333
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发表时间：
2014-01-21
期刊：
影响因子：
3.7
通讯作者：
Engler, Harald
中科院分区：
文献类型：
--
作者：
Gola, Hannah;Engler, Andrea;Engler, Harald
背景：创伤后应激障碍（PTSD）是一种严重的精神疾病，被发现与下丘脑-垂体-肾上腺（HPA）轴功能改变和糖皮质激素（GC）反应性改变有关。GC的生理作用主要是通过GC受体介导的，GC受体具有不同的生物活性。本研究旨在探讨创伤经历和/或创伤后应激障碍是否与GR剪接变异体表达改变有关。方法：采用实时荧光定量PCR技术检测慢性、重度PTSD患者（n=42）和种族匹配对照（n= 35）全血中GR α和GR β mRNA的表达水平。结果：与非PTSD受试者相比，PTSD患者表现出明显较低的显性和功能活跃的GR α亚型表达。当考虑到性别、吸烟、精神药物或共病性抑郁症时，这种影响仍然显著。此外，在整个样本和PTSD患者组中，GR α表达水平与经历的创伤事件类型数量呈显著负相关。较少丰度和非配体结合的GR β亚型的表达在患者组和参照组之间具有可比性。结论：创伤后应激障碍患者外周血细胞功能活性GR α亚型的表达减少似乎是创伤负担的累积效应，而不是创伤后应激障碍的特定特征，因为高创伤负荷的非创伤后应激障碍受试者表现出介于创伤后应激障碍患者和没有或很少创伤经历的个体之间的中间表型。
Background: Posttraumatic stress disorder (PTSD) is a serious psychiatric condition that was found to be associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid (GC) responsiveness. The physiological actions of GCs are primarily mediated through GC receptors (GR) of which isoforms with different biological activities exist. This study aimed to investigate whether trauma-experience and/or PTSD are associated with altered expression of GR splice variants.Methods: GR alpha and GR beta mRNA expression levels were determined by real-time quantitative PCR in whole blood samples of individuals with chronic and severe forms of PTSD (n=42) as well as in ethnically matched reference subjects (non-PTSD, n=35).Results: Individuals suffering from PTSD exhibited significantly lower expression of the predominant and functionally active GR alpha isoform compared to non-PTSD subjects. This effect remained significant when accounting for gender, smoking, psychotropic medication or comorbid depression. Moreover, the GR alpha expression level was significantly negatively correlated with the number of traumatic event types experienced, both in the whole sample and within the PTSD patient group. Expression of the less abundant and non-ligand binding GR beta isoform was comparable between patient and reference groups.Conclusions: Reduced expression of the functionally active GR alpha isoform in peripheral blood cells of individuals with PTSD seems to be a cumulative effect of trauma burden rather than a specific feature of PTSD since non-PTSD subjects with high trauma load showed an intermediate phenotype between PTSD patients and individuals with no or few traumatic experiences.