Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, United States of America.
Department of Psychology, The Hebrew University of Jerusalem, Jerusalem, Israel.
PLoS One. 2020 Apr 3;15(4):e0221310. doi: 10.1371/journal.pone.0221310. eCollection 2020.
Exposure to early-life adversity (ELA) can result in long-term changes to physiological systems, which predispose individuals to negative health outcomes. This biological embedding of stress-responsive systems may operate via dysregulation of physiological resources in response to common stressors. The present pilot study outlines a novel experimental design to test how young adults' exposure to ELA influences neuroendocrine and inflammatory responses to acute stress.
Participants were 12 males (mean age = 21.25), half of whom endorsed at least three significant adverse events up to age 18 years ('ELA group'), and half who confirmed zero ('controls'). Using a randomized within-subjects, between-groups experimental design, we induced acute psychosocial stress (Trier Social Stress Test, TSST), and included a no-stress control condition one week apart. During these sessions, we obtained repeated measurements of physiological reactivity, gene expression of the glucocorticoid receptor (NR3C1), and plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) over a 4-hour window post-test.
In this pilot study, the ELA group evinced higher cortisol response and blunted NR3C1 gene expression in response to the TSST compared with controls, while no differences were observed in the no-stress condition. For pro-inflammatory cytokines, only IL-6 increased significantly in response to the TSST, with no differences between the two groups.
Overall, this pilot feasibility study provides a framework to investigate the biological embedding of early-adversity via dysregulation across physiological and genomic systems in response to acute psychosocial stress. ELA may program such systems in a maladaptive manner more likely to manifest during times of duress, predisposing individuals to the negative health consequences of everyday stressors. Future studies with larger sample size including both males and females are needed to replicate and expand upon these preliminary findings.
早期生活逆境（ELA）的暴露会导致生理系统的长期变化，使个体易患负面健康结果。应激反应系统的这种生物嵌入可能通过对常见应激源的生理资源的失调来发挥作用。本初步研究概述了一种新的实验设计，以测试年轻人暴露于 ELA 如何影响神经内分泌和炎症对急性应激的反应。
参与者为 12 名男性（平均年龄=21.25 岁），其中一半人在 18 岁之前至少经历过三次重大不良事件（“ELA 组”），另一半人则确认没有（“对照组”）。使用随机的、个体内、组间实验设计，我们诱发了急性社会心理应激（Trier 社会应激测试，TSST），并在一周后增加了一个无应激对照条件。在这些会议期间，我们在 4 小时的测试后窗口内获得了生理反应、糖皮质激素受体（NR3C1）基因表达和促炎细胞因子（IL-1β、IL-6、IL-8 和 TNFα）的血浆水平的重复测量。
在这项初步研究中，与对照组相比，ELA 组在 TSST 应激下表现出更高的皮质醇反应和 NR3C1 基因表达的迟钝，而在无应激条件下则没有观察到差异。对于促炎细胞因子，只有 IL-6 对 TSST 有显著增加，两组之间没有差异。
总体而言，这项初步可行性研究为通过生理和基因组系统对急性社会心理应激的失调来研究早期逆境的生物嵌入提供了一个框架。ELA 可能以一种适应不良的方式对这些系统进行编程，更有可能在压力时期表现出来，使个体易患日常应激源的负面健康后果。需要进行更大规模的研究，包括男性和女性，以复制和扩展这些初步发现。
