Association Among Clinical Response, Hippocampal Volume, and FKBP5 Gene Expression in Individuals with Posttraumatic Stress Disorder Receiving Cognitive Behavioral Therapy
Association Among Clinical Response, Hippocampal Volume, and FKBP5 Gene Expression in Individuals with Posttraumatic Stress Disorder Receiving Cognitive Behavioral Therapy
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DOI：
10.1016/j.biopsych.2013.05.017
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发表时间：
2013-12-01
影响因子：
10.6
通讯作者：
Keri, Szabolcs
中科院分区：
文献类型：
--
作者：
Levy-Gigi, Einat;Szabo, Csilla;Keri, Szabolcs
背景：创伤后应激障碍(PTSD)的特征是糖皮质激素受体的关键调节因子FKBP5的表达减少。较小的海马体体积也被记录在创伤后应激障碍中。探讨PTSD患者认知行为治疗(CBT)后FKBP5基因表达和脑结构的变化。方法：测定39例PTSD患者CBT治疗前后外周血中FKBP5基因表达和脑结构的变化，并对其海马区、杏仁体和眶前内侧皮质的体积进行测定。对照受试者是31名没有创伤后应激障碍的创伤暴露者，他们也接受了两次评估。用基因芯片技术筛选基因表达变化，然后用定量聚合酶链式反应检测FKBP5RNA。结果：与对照组相比，PTSD患者FKBP5基因表达降低，海马区和内侧眶前叶皮质体积变小，但杏仁核体积无明显变化。在随访中，我们发现创伤后应激障碍患者FKBP5表达显著增加，海马体体积增加。在随访时，患者的海马体体积与对照组没有差别。创伤后应激障碍症状的改善是通过增加FKBP5的表达和增加海马体积来预测的，但主要的预测因素是FKBP5的表达。与对照组相比，PTSD患者核糖体蛋白S6激酶基因表达变化最显著，CBT后该基因表达无明显变化，且与海马区体积无关。结论：PTSD患者临床症状的改善与FKBP5表达增加和海马区体积增大呈正相关。
Background: Posttraumatic stress disorder (PTSD) is characterized by a reduced expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller hippocampal volume has also been documented in PTSD. We explored possible changes in FKBP5 gene expression and brain structure in patients with PTSD after cognitive behavioral therapy (CBT).Methods: We measured peripheral FKBP5 RNA and volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39 patients with PTSD before and after CBT. The control subjects were 31 trauma-exposed individuals without PTSD who were also assessed twice. Gene expression changes were screened with a microarray toolkit, which was followed by quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured using FreeSurfer.Results: At baseline, patients with PTSD showed lower FKBP5 gene expression and smaller hippocampal and medial orbitofrontal cortex, but not amygdala, volumes relative to control subjects. At follow-up, we found significantly increased FKBP5 expression and increased hippocampal volume in patients with PTSD. At follow-up, patients did not differ from control subjects in hippocampal volume. Improvement in PTSD symptoms was predicted by increased FKBP5 expression and increased hippocampal volume, but the primary predictor was FKBP5 expression. The most significantly altered gene expression in patients with PTSD relative to control subjects was found for ribosomal protein S6 kinase, which did not change after CBT and did not correlate with hippocampal volume.Conclusions: Clinical improvement in individuals with PTSD was associated with increased expression of FKBP5 and increased hippocampal volume, which were positively correlated.