Kuhlman Kate Ryan, Tan Ece N, Cole Steve W, Rao Uma
Department of Psychological Science, School of Social Ecology, University of California Irvine, Irvine, CA, USA; Department of Population Health and Disease Prevention, Program in Public Health, University of California Irvine, Irvine, CA, USA; Cousins Center for Psychoneuroimmunology, Semel Institute of Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry & Human Behavior, School of Medicine, University of California Irvine, Irvine, CA, USA.
Brain Behav Immun. 2025 Jul;127:183-192. doi: 10.1016/j.bbi.2025.03.004. Epub 2025 Mar 8.
Psychosocial stress has been linked to myriad mental and physical health conditions. Stress-induced changes to functioning of the immune system is a plausible mechanism in this association. Psychosocial stress is a well-established contributor to immune dysregulation, though the extant literature to date falls short of addressing the role of distal relative to contemporary stress in immune function, particularly as they relate to distinctions between innate and adaptive immunity. The present study directly addressed this knowledge gap by characterizing vertically-integrated markers of immune functioning as a function of both recent chronic stress during adolescence and childhood adversity. In the present study, childhood adversity (before age 10) and recent psychosocial stressors (past 6 months) were characterized via semi-structured clinical interviews among 127 adolescent girls (aged 13-17; 31 % Black, 38 % Hispanic, 32 % NHW) who have all measures included in this report. Vertically-integrated markers of immune activity were also collected: an a priori subset of immune-related genes using genome-wide transcriptional profiling, an 11-plex of circulating cytokines (IL-6, TNF-α, IL-10, IL-8, IFN-γ, IL-1β, IL-1α, IL-27, MCP-1, IL-12p70, IP-10), and systemic inflammation (C-reactive protein; CRP). The association between recent chronic stress and intracellular immune outcomes differed based on childhood adversity. Genome-wide transcriptional profiling implicated myeloid lineage cells, specifically monocytes and dendritic cells, in differential patterns of gene expression among childhood adversity-exposed youth in the context of chronic stress. These differential patterns were also reflected in expression of proinflammatory genes and CRP such that among adolescents without exposure to childhood adversity, more recent chronic stress was associated with less proinflammatory gene expression, b = -0.45 (SE = 0.22), p = 0.04, 95 %CI [-0.87, -0.02], and somewhat higher CRP, b = 0.62 (SE = 0.35), p = 0.08, 95 %CI [-0.07, 1.31], while among adolescents with exposure to childhood adversity, more recent chronic stress was not associated with any immune activity markers. However, these patterns among circulating markers did not survive corrections for multiple comparisons. Immune adaptation in the context of chronic stress may indicate plasticity to environmental demands that conserves biological resources, which may be a source of resilience that is negatively impacted by childhood adversity.
心理社会压力与众多身心健康状况相关联。压力诱导免疫系统功能的变化是这种关联中一个合理的机制。心理社会压力是免疫失调的一个公认因素，尽管迄今为止的现有文献未能探讨相对于当代压力而言，远期压力在免疫功能中的作用，尤其是它们与先天免疫和适应性免疫之间区别的关系。本研究通过将免疫功能的纵向整合标志物表征为青少年时期近期慢性压力和童年逆境的函数，直接填补了这一知识空白。在本研究中，通过对127名青春期女孩（年龄13 - 17岁；31%为黑人，38%为西班牙裔，32%为非西班牙裔白人）进行半结构化临床访谈，对童年逆境（10岁之前）和近期心理社会压力源（过去6个月）进行了表征，本报告涵盖了她们的所有测量数据。还收集了免疫活动的纵向整合标志物：使用全基因组转录谱分析的一组先验免疫相关基因、一组11种循环细胞因子（IL - 6、TNF -α、IL - 10、IL - 8、IFN -γ、IL - 1β、IL - 1α、IL - 27、MCP - 1、IL - 12p70、IP - 10）以及全身炎症（C反应蛋白；CRP）。近期慢性压力与细胞内免疫结果之间的关联因童年逆境而异。全基因组转录谱分析表明，在慢性压力背景下，骨髓系细胞，特别是单核细胞和树突状细胞，在童年逆境暴露青少年的基因表达差异模式中起作用。这些差异模式也反映在促炎基因和CRP的表达中，即在未暴露于童年逆境的青少年中，近期慢性压力与较少的促炎基因表达相关，b = -0.45（标准误 = 0.22），p = 0.04，95%置信区间[-0.87, -0.02]，以及略高的CRP，b = 0.62（标准误 = 0.35），p = 0.08，95%置信区间[-0.07, 1.31]，而在暴露于童年逆境的青少年中，近期慢性压力与任何免疫活动标志物均无关联。然而，这些循环标志物中的模式在多重比较校正后并不成立。慢性压力背景下的免疫适应可能表明对环境需求的可塑性，这种可塑性可保存生物资源，这可能是一种恢复力的来源，但会受到童年逆境的负面影响。
