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

Zirui ZHANG; Hong SHI; Wanyang LEI; Weijia CHEN; Letian TANG; Jing LI; Xueshan XIA

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Zirui ZHANG, Hong SHI, Wanyang LEI, Weijia CHEN, Letian TANG, Jing LI, Xueshan XIA. Childhood Adverse Events and Their Correlation with FKBP5，ACTH，BDNF，and Cortisol in Susceptible and Resilient Drug-using Populations[J]. Journal of Kunming Medical University.

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

Zirui ZHANG^{1, 2},
Hong SHI³,
Wanyang LEI^{1, 2},
Weijia CHEN³,
Letian TANG^{1, 2},
Jing LI^{1, 2
,
,},
Xueshan XIA^{1, 2
,
,}

1.
Yunnan Provincial Key Laboratory of Public Health and Biosafety/School of Public Health，Kunming Medical University，Kunming Yunnan 650500
2.
Yunnan Provincial Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development/School of Public Health，Kunming Medical University，Kunming Yunnan 650500
3.
Institute of Primate Translational Medicine，Kunming University of Science and Technology，Kunming Yunnan 650500，China

Received Date: 2026-04-20
Available Online: 2026-06-04

Abstract

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.n 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.
- Adverse childhood experiences,
- FKBP5,
- ACTH,
- Resilience,
- Susceptibility

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References(54)

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