精神应激障碍相关免疫功能紊乱的检测、机制探讨、及药物干预效果检验

Prior research has indicated that besides psychological alterations, trauma experience may scar people by systemically and chronically disrupting the body function. Indeed, based on population-based register data from Sweden, the association between stress-related disorder and subsequent autoimmune disease has been, for the first time, clearly demonstrated in the applicant’s recent JAMA paper. Together with our following studies showing increased susceptibility to infectious diseases among traumatized populations, we have a strong rationale to hypothesize that stress-related disorders could have an influential and prolonged effect on the human immune system. In this proposal, the applicant aims to have an in-depth exploration of stress-related immune dysfunction, with research focus placed on the biological basis of stress-immunity pathway, and the possibility of breaking this pathway through pharmacotherapy of stress-related disorder. The applicant will achieve this aim by 1) detecting clinical biomarkers of immune dysfunction among PTSD patients using historical medical records from West China Hospital of Sichuan University ; 2) examining whether PTSD due to Wenchuan earthquake experience can lead to long-term alteration in immune system through a 12-year follow-up of these traumatized individuals, and if such an effect can be explained by specific epigenetic profiles,; 3) elucidating genetic shares between stress-related disorder and certain autoimmune disease, using published summary statistics of GWAS data; 4) disentangling if the use of selective serotonin reuptake inhibitors (SSRIs) can reduce the stress-associated immune dysfunction, by monitoring the dynamic changes of inflammatory cytokines and DNA methylation of immune-related genes with SSRI use, in a prospective clinical study. This research program has a potential to significantly advance our knowledge of the biologic mechanisms of stress-associated immune dysfunction. Moreover, our efforts on demonstrating immunological improvement with SSRI treatment have important clinical significance, by showing effective treatment of stress-related disorder might not only lessen psychiatric symptoms, but also benefit patients in terms of reducing their further risk of health decline.

近期诸多国内外研究将暴露于创伤性事件后出现的精神应激障碍对人体整体健康的负面影响进行了新的诠释, 使精神应激障碍，包括创伤后应激障碍（PTSD），成为精神疾病领域新的研究热点和难点。在申请人最近发表的JAMA论文中，使用瑞典的健康数据库，精神应激障碍与随后的自身免疫疾病的相关性首次在普通公共人群中得到了明确证实。此外，我们的后续数据研究还显示，创伤人群对传染性疾病的易感性也明显增加。这些证据使我们作出假设：精神应激障碍可能对人体免疫系统有显著和长期的影响。本研究拟整合多种资源（临床历史数据、地震灾区现场流行病病例对照数据、临床前瞻性研究数据），从不同生理层面（细胞、基因表达、及基因）展示和探索由精神应激障碍所引起的躯体免疫相关变化。另外，我们将重点验证对精神应激障碍治疗，尤其是药物治疗，是否可以改善由应激障碍引起的免疫功能障碍，以加强公众对精神应激障碍诊断和治疗重要性的认识。

内容获取失败，请点击重试