Rudzki Stephan
Canberra Sports Medicine, Deakin, Australian Capital Territory 2600, Australia.
Mil Med. 2023 Jul 22;188(7-8). doi: 10.1093/milmed/usac095. Epub 2022 Apr 21.
Treatment outcomes for PTSD with current psychological therapies are poor, with very few patients achieving sustained symptom remission. A number of authors have identified physiological and immune disturbances in Post Traumatic Stress Disorder (PTSD) patients, but there is no unifying hypothesis that explains the myriad features of the disorder.
The medical literature was reviewed over a 6-year period primarily using the medical database PUBMED.
The literature contains numerous papers that have identified a range of physiological and immune dysfunction in association with PTSD. This paper proposes that unrestrained cytokine signaling induces epigenetic changes that promote an evolutionary survival adaptation, which maintains a defensive PTSD phenotype. The brain can associate immune signaling with past threat and initiate a defensive behavioral response. The sympathetic nervous system is pro-inflammatory, while the parasympathetic nervous system is anti-inflammatory. Prolonged cholinergic withdrawal will promote a chronic inflammatory state. The innate immune cytokine IL-1β has pleiotropic properties and can regulate autonomic, glucocorticoid, and glutamate receptor functions, sleep, memory, and epigenetic enzymes. Changes in epigenetic enzyme activity can potentially alter phenotype and induce an adaptation. Levels of IL-1β correlate with severity and duration of PTSD and PTSD can be prevented by bolus administration of hydrocortisone in acute sepsis, consistent with unrestrained inflammation being a risk factor for PTSD. The nervous and immune systems engage in crosstalk, governed by common receptors. The benefits of currently used psychiatric medication may arise from immune, as well as synaptic, modulation. The psychedelic drugs (3,4-Methylenedioxymethamphetamine (MDMA), psilocybin, and ketamine) have potent immunosuppressive and anti-inflammatory effects on the adaptive immune system, which may contribute to their reported benefit in PTSD. There may be distinct PTSD phenotypes induced by innate and adaptive cytokine signaling.
In order for an organism to survive, it must adapt to its environment. Cytokines signal danger to the brain and can induce epigenetic changes that result in a persistent defensive phenotype. PTSD may be the price individuals pay for the genomic flexibility that promotes adaptation and survival.
目前的心理疗法对创伤后应激障碍（PTSD）的治疗效果不佳，只有极少数患者能实现症状持续缓解。许多作者已确定创伤后应激障碍（PTSD）患者存在生理和免疫紊乱，但尚无统一假说来解释该疾病的众多特征。
主要通过医学数据库PUBMED对6年期间的医学文献进行了综述。
文献中有大量论文指出与PTSD相关的一系列生理和免疫功能障碍。本文提出不受抑制的细胞因子信号传导会诱导表观遗传变化，从而促进一种进化生存适应，维持防御性PTSD表型。大脑可将免疫信号与过去的威胁联系起来，并引发防御性行为反应。交感神经系统具有促炎作用，而副交感神经系统具有抗炎作用。长期胆碱能缺乏会促进慢性炎症状态。先天性免疫细胞因子白细胞介素-1β（IL-1β）具有多效性，可调节自主神经、糖皮质激素和谷氨酸受体功能、睡眠、记忆及表观遗传酶。表观遗传酶活性的变化可能会改变表型并诱导适应。IL-1β水平与PTSD的严重程度和持续时间相关，在急性脓毒症中通过大剂量注射氢化可的松可预防PTSD，这与不受抑制的炎症是PTSD的一个危险因素相一致。神经和免疫系统通过共同受体进行相互作用。目前使用的精神科药物的益处可能源于免疫调节以及突触调节。迷幻药物（3,4-亚甲基二氧甲基苯丙胺（摇头丸）、裸盖菇素和氯胺酮）对适应性免疫系统具有强大的免疫抑制和抗炎作用，这可能是其在PTSD中显示出益处的原因。先天性和适应性细胞因子信号传导可能会诱导不同的PTSD表型。
为了生存，生物体必须适应其环境。细胞因子向大脑发出危险信号，并可诱导表观遗传变化，从而导致持续的防御表型。PTSD可能是个体为促进适应和生存的基因组灵活性所付出的代价。
