Supplementary Material for: Plasma allopregnanolone and sex hormone responses to stress induction: contributors to the formation of intrusive memories

Introduction: Intrusive memories are a central identifying symptom of post-traumatic stress disorder (PTSD), and their development can be modelled in experimental settings with the trauma film paradigm. Neurosteroids and sex hormones such as allopregnanolone and testosterone, respectively, have recently become potential targets for PTSD pharmacological treatment due to their influence on the stress response. Methods: In the current study 49 healthy female participants underwent stress induction and viewed a trauma film. Plasma allopregnanolone, testosterone, and cortisol responses to stress induction and the trauma film were recorded and stress-induced responses were modelled as predictors of intrusive memory frequency using negative binomial regression models. Results: Compared to baseline, plasma allopregnanolone and cortisol levels, along with subjective stress, were significantly higher after the stress induction. Plasma cortisol and subjective stress responses to the stress induction task significantly predicted intrusive memories. Allopregnanolone and testosterone did not predict intrusive memories, though allopregnanolone and cortisol stress responses were significantly correlated. Discussion: These findings expand our current understanding of the biochemical processes of intrusive memory formation under stress. Additionally, changes in allopregnanolone were observed in response to stress, which contributes towards the discussion of neurosteroids and sex hormones as potential pharmacological targets for the treatment of PTSD.

引言：侵入性记忆（intrusive memories）是创伤后应激障碍（post-traumatic stress disorder, PTSD）的核心标志性症状，可借助创伤电影范式（trauma film paradigm）在实验环境中对其发生发展过程进行建模。近年来，别孕烷醇酮（allopregnanolone）、睾酮（testosterone）这类神经甾体与性激素，因其对机体应激反应具有调控作用，成为创伤后应激障碍药物治疗的潜在靶点。方法：本研究纳入49名健康女性受试者，先对其实施应激诱导处理，随后让其观看创伤电影。研究记录了受试者血浆中别孕烷醇酮、睾酮与皮质醇（cortisol）对应激诱导及创伤电影的反应水平，并采用负二项回归模型（negative binomial regression models），将应激诱导产生的生理反应作为侵入性记忆频率的预测因子开展建模分析。结果：与基线水平相比，应激诱导完成后，受试者血浆中别孕烷醇酮、皮质醇水平以及主观应激水平均显著升高。对应激诱导任务的血浆皮质醇反应与主观应激水平，可显著预测侵入性记忆的发生频率。别孕烷醇酮与睾酮则未表现出对侵入性记忆的预测作用，但别孕烷醇酮与皮质醇的应激反应呈显著相关。讨论：本研究结果拓展了当前对应激状态下侵入性记忆形成的生化过程的认知。此外，本研究观测到别孕烷醇酮水平会随应激刺激发生显著变化，为神经甾体与性激素作为创伤后应激障碍潜在药物治疗靶点的相关学术讨论提供了实证支撑。