Association Between Childhood Maltreatment, FKBP5 Gene Methylation, and Anxiety Symptoms Among Chinese Adolescents: A Nested Case-Control Study

BACKGROUND: Anxiety symptoms are common mental health problems among adolescents worldwide. This study aimed to explore (1) the longitudinal association between childhood maltreatment and anxiety symptoms, (2) the association between childhood maltreatment and DNA methylation of the FKBP5 gene, and (3) the association of DNA methylation of the FKBP5 gene with anxiety symptoms at follow-up. METHODS: A nested case-control design was conducted to identify a case group and control group from a longitudinal study of adolescents aged 13–18 years in Guangzhou from 2019 to 2020. Adolescents with anxiety symptoms at baseline and follow-up were considered the case group, while those without anxiety symptoms at baseline and follow-up were considered the control group. The case and control groups were matched according to age and sex. Our study finally included 97 cases and 141 controls. RESULTS: After adjusting for significant covariates, childhood emotional abuse was associated with subsequent anxiety symptoms (β = 0.146, 95% CI = 0.010~0.283); students with physical and emotional neglect were more likely to get a lower level of DNA methylation at most CpG units of FKBP5 gene (P < 0.05); FKBP5-12 CpG 15 methylation was associated with anxiety symptoms at follow-up (β = −0.263, 95% CI = −0.458~-0.069). However, after multiple hypothesis testing, childhood maltreatment was not associated with FKBP5 DNA methylation (q > 0.10); FKBP5 DNA methylation did not show an association with subsequent anxiety symptoms (q > 0.10). CONCLUSIONS: Childhood emotional abuse was associated with an increased risk of anxiety symptoms among Chinese adolescents. After multiple hypothesis testing, childhood maltreatment was not significantly associated with FKBP5 DNA methylation. DNA methylation of the promoter region of the FKBP5 gene was not a significant predictor of anxiety symptoms. More attention should be paid to the mental health of adolescents with childhood maltreatment.