Clinical Psychopharmacology Unit, Research Dept of Clinical, Educational and Health Psychology, University College London, Gower St, London, WC1E 6BT, UK.
Department of Anaesthesia and Perioperative Medicine, University College London Hospital, London, NW1 2BU, UK.
Transl Psychiatry. 2022 Aug 31;12(1):354. doi: 10.1038/s41398-022-02126-2.
Posttraumatic stress disorder (PTSD) is characterised by dysregulated hypothalamic-pituitary-adrenal axis activity and altered glucocorticoid receptor sensitivity. Early treatment with glucocorticoids may reduce PTSD risk, although the effect of such treatment on the aetiologically critical step of traumatic-memory-formation remains unclear. Here we examine the effects of exogenous cortisol (hydrocortisone) in a preclinical model of PTSD, using a factorial (Drug × Sex), randomised-controlled, double-blind design. Healthy men and women (n = 120) were randomised to receive 30 mg oral hydrocortisone or matched placebo immediately after watching a stressful film. Effects on film-related intrusions were assessed acutely in the lab, and ecologically using daily memory diaries for one week. We found that participants receiving hydrocortisone showed a faster reduction in daily intrusion frequency. Voluntary memory was assessed once, at the end of the week, but was unaffected by hydrocortisone. Exploratory analyses indicated sex-dependent associations between intrusions and baseline estradiol and progesterone levels. In men receiving hydrocortisone, higher baseline estradiol levels were associated with fewer intrusions, whereas women exhibited the opposite pattern. By contrast, progesterone levels were positively associated with intrusions only in men treated with hydrocortisone. The findings suggest that hydrocortisone promotes an accelerated degradation of sensory-perceptual representations underlying traumatic intrusive memories. In addition, while sex alone was not an important moderator, the combination of sex and sex-hormone levels (especially estradiol) influenced hydrocortisone's effects on involuntary aversive memories. Future well-powered experimental studies may provide a basis for a precision-psychiatry approach to optimising early post-traumatic glucocorticoid treatments that target intrusive memories, based on individual endocrinological profiles.
创伤后应激障碍（PTSD）的特征是下丘脑-垂体-肾上腺轴活动失调和糖皮质激素受体敏感性改变。早期使用糖皮质激素治疗可能会降低 PTSD 的风险，尽管这种治疗对创伤性记忆形成这一关键病因步骤的影响尚不清楚。在这里，我们使用因子（药物×性别）、随机对照、双盲设计，在 PTSD 的临床前模型中检查了外源性皮质醇（氢化可的松）的作用。健康男性和女性（n=120）随机接受 30mg 口服氢化可的松或匹配的安慰剂，在观看压力电影后立即服用。在实验室中急性评估对电影相关侵入的影响，并使用一周的每日记忆日记进行生态评估。我们发现，接受氢化可的松治疗的参与者每日侵入频率的下降速度更快。自愿记忆仅在一周结束时评估一次，但不受氢化可的松的影响。探索性分析表明，侵入与基线雌二醇和孕酮水平之间存在性别依赖性关联。在接受氢化可的松治疗的男性中，较高的基线雌二醇水平与较少的侵入有关，而女性则表现出相反的模式。相比之下，只有接受氢化可的松治疗的男性中，孕酮水平与侵入呈正相关。研究结果表明，氢化可的松促进了创伤性侵入性记忆的感觉知觉表现的快速降解。此外，尽管性别本身不是一个重要的调节因素，但性别和性激素水平（尤其是雌二醇）的组合影响了氢化可的松对无意识厌恶记忆的作用。未来的大型实验研究可能为基于个体内分泌谱优化针对侵入性记忆的创伤后早期糖皮质激素治疗的精准精神病学方法提供基础。
