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糖皮质激素受体基因常见多态性与重症监护治疗后患者创伤记忆和创伤后应激障碍的关系。

Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy.

机构信息

Departments of Anaesthesiology, Ludwig-Maximilians University, Munich, Germany.

出版信息

Crit Care Med. 2011 Apr;39(4):643-50. doi: 10.1097/CCM.0b013e318206bae6.

Abstract

OBJECTIVE

Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. They act through the glucocorticoid receptor, for which, in humans, several polymorphisms have been described. In particular, the BclI single-nucleotide polymorphism is associated with hypersensitivity to glucocorticoids and with susceptibility to development of major depression. Furthermore, in patients with posttraumatic stress disorder carrying the BclI GG genotype, cortisol levels were lower and showed an inverse relationship to posttraumatic stress disorder symptom intensity. Here, we studied the association of the BclI polymorphism with plasma cortisol levels, traumatic memories, posttraumatic stress disorder symptoms, and health-related quality of life outcomes in 126 patients undergoing cardiac surgery and intensive care unit therapy.

DESIGN

Prospective observational study.

SETTING

Cardiovascular intensive care unit in a university hospital.

PATIENTS

A total of 126 patients undergoing cardiac surgery and intensive care unit treatment.

INTERVENTIONS

No interventions were performed.

MEASUREMENTS AND MAIN RESULTS

Validated questionnaires were used to quantify end points. Measurements were taken 1 day before and 1 wk and 6 months after cardiac surgery. Homozygous carriers of the BclI G allele (n = 21) had significantly lower preoperative plasma cortisol levels and more long-term traumatic memories from intensive care unit therapy at 6 months after cardiac surgery than heterozygous carriers or noncarriers (1.9 ± 1.4 vs. 1.0 ± 1.2, p = .01). Anxiety was significantly more common as a long-term traumatic memory in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers (57% vs. 35%, p = .03). Posttraumatic stress disorder symptom scores were significantly higher at discharge from the intensive care unit in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers. Only heterozygous carriers or BclI G allele noncarriers had a significant gain in health-related quality of life physical function at 6 months after cardiac surgery (p < .01). Baseline values were not statistically different between carriers of the different BclI alleles.

CONCLUSION

Homozygous BclI G allele carriers are at risk for traumatic memories, posttraumatic stress disorder symptoms, and lower health-related quality of life after cardiac surgery and intensive care unit therapy. The BclI single-nucleotide polymorphism may help to identify individuals at need for tailored medical care.

摘要

目的

糖皮质激素在创伤信息的巩固和提取中起着重要作用。它们通过糖皮质激素受体发挥作用,人类已经描述了几种该受体的多态性。特别是,BclI 单核苷酸多态性与糖皮质激素的超敏性和易患重度抑郁症有关。此外,携带 BclI GG 基因型的创伤后应激障碍患者,其皮质醇水平较低,并与创伤后应激障碍症状严重程度呈负相关。在这里,我们研究了 BclI 多态性与血浆皮质醇水平、创伤性记忆、创伤后应激障碍症状以及 126 例接受心脏手术和重症监护治疗的患者的健康相关生活质量结果之间的关系。

设计

前瞻性观察研究。

地点

大学医院心血管重症监护病房。

患者

共 126 例接受心脏手术和重症监护治疗的患者。

干预

未进行干预。

测量和主要结果

使用验证后的问卷来量化终点。测量于心脏手术后 1 天、1 周和 6 个月进行。BclI G 等位基因纯合子(n = 21)患者的术前血浆皮质醇水平显著较低,并且在心脏手术后 6 个月时 ICU 治疗的长期创伤性记忆更多,与杂合子或非携带者相比(1.9 ± 1.4 对 1.0 ± 1.2,p =.01)。焦虑作为 BclI G 等位基因纯合子携带者的长期创伤性记忆更为常见,而非杂合子或非携带者(57%对 35%,p =.03)。BclI G 等位基因纯合子携带者在离开重症监护病房时的创伤后应激障碍症状评分显著高于杂合子或非携带者。只有杂合子或 BclI G 等位基因非携带者在心脏手术后 6 个月时健康相关生活质量的身体功能有显著改善(p <.01)。不同 BclI 等位基因携带者的基线值无统计学差异。

结论

BclI G 等位基因纯合子携带者在心脏手术后和重症监护治疗后存在创伤性记忆、创伤后应激障碍症状和较低的健康相关生活质量的风险。BclI 单核苷酸多态性可能有助于识别需要个体化医疗护理的个体。

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