易感与弹性吸毒人群的童年期负性事件与FKBP5、ACTH、BDNF和皮质醇的相关性

Childhood Adverse Events and Their Correlation with FKBP5，ACTH，BDNF，and Cortisol in Susceptible and Resilient Drug-using Populations

摘要

目的 探讨童年期负性事件与不良健康结局的关联，比较在童年期负性事件暴露下易感与弹性个体在FKBP5、ACTH、皮质醇、BDNF的差异。方法 基于前期2021年1月至2021年7月建立的云南省405例吸毒人群的队列，采用巢式病例对照研究，检测对照组、弹性组及易感组的FKBP5、ACTH、皮质醇和BDNF水平；采用全基因组测序（whole genome sequencing，WGS）技术确定突变位点；运用SPSS 24.0和RStudio 4.3.1进行统计描述及多因素分析。结果 对照组（n = 7）与弹性组（n = 14）的FKBP5水平存在显著差异[（4.67±1.08） vs. （6.86±1.87） ng/mL，P ＜ 0.05]。与对照组相比，易感组（n = 14）的ACTH水平升高[（54.05±8.75） pg/mL，P ＜ 0.05]；与易感组相比，弹性组的ACTH水平升高[（67.28±8.36） pg/mL，P ＜ 0.05]。皮质醇水平在对照组与易感组[（254.92±70.46） vs. （278.50±49.60） nmol/L，P ＜ 0.05]以及易感组与弹性组[（278.50±49.60） vs. （406.27±72.07） nmol/L，P ＜ 0.05]之间均存在显著差异。多元Logistic回归分析显示，以对照组为参照，弹性组的FKBP5、皮质醇及rs34224676基因型水平均存在显著差异（OR = 3.62，95%CI：1.36～9.64，P ＜ 0.05；OR = 1.02，95%CI：1.00～1.04，P ＜ 0.05；OR = 185.34，95%CI：69.56～493.83，P ＜ 0.05）。结论 有ACEs暴露的吸毒人群FKBP5、ACTH和皮质醇水平高于无ACEs暴露者。在ACEs暴露下，吸毒人群中FKBP5、皮质醇及SNPs位点rs34224676的表达可能与弹性现象有关。

Abstract

Objective To investigate the association between adverse childhood experiences (ACEs) and adverse health outcomes (AHOs)，and to compare the levels of FKBP5，ACTH，cortisol，and BDNF between susceptible and resilient individuals exposed to ACEs during childhood. Methods Based on a cohort of 405 individuals with substance use disorder in Yunnan Province established from January to July 2021，a nested case-control study was conducted. FKBP5，ACTH，cortisol，and BDNF levels were detected in the control group，resilient group and susceptible group. Whole-genome sequencing (WGS) technology was used to identify mutation sites. Descriptive，univariate and multivariate analyses were conducted using SPSS 24.0 and R Studio version 4.3.1. Results Significant differences in FKBP5 levels were found between the control group (n = 7) and resilient groups (n = 14) [(4.67±1.08) vs. (6.86±1.87) ng/mL，P ＜ 0.05]. Compared with the control group，ACTH levels in the susceptible group (n = 14) were elevated [(54.05±8.75) pg/mL，P ＜ 0.05]; compared with the susceptible group，ACTH levels in the resilient group were elevated [(67.28±8.36) pg/mL，P ＜ 0.05]. Cortisol levels showed significant differences between the control and susceptible groups [(254.92±70.46) vs. (278.50±49.60) nmol/L，P ＜ 0.05] and between the susceptible and resilient groups [(278.50±49.60) vs. (406.27±72.07) nmol/L，P ＜ 0.05]. Multivariate logistic regression analysis showed that，with the control group as reference，the resilient group had significant differences in FKBP5，cortisol，and rs34224676 genotype levels (OR = 3.62，95%CI: 1.36～9.64，P ＜ 0.05; OR = 1.02，95%CI: 1.00～1.04，P ＜ 0.05; OR = 185.34，95%CI: 69.56～493.83，P ＜ 0.05). Conclusion Individuals with substance use disorder exposed to ACEs exhibited higher levels of FKBP5，ACTH，and cortisol compared to those without ACEs exposure. Under ACEs exposure，the expression of FKBP5，cortisol，and the SNP locus rs34224676 in individuals with substance use disorder may be associated with the resilience phenomena.

关键词

童年期负性事件 / FKBP5 / ACTH / 弹性 / 易感性

Key words

Adverse childhood experiences / FKBP5 / ACTH / Resilience / Susceptibility

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基金资助

云南省应用基础研究项目(202301AY070001-258)

国家自然科学基金(72274086)

云南省中青年学术和技术带头人后备人才项目(202205AC160064)

昆明医科大学一流学科团队(2024XKTDYS09)