Prolonged parent-child separation and pain in adolescence: The role of HPA-axis genetic variations.

ABSTRACT

BACKGROUND: Increasing evidence has demonstrated that childhood adversity was a predictor of pain and hypothalamic-pituitary-adrenal (HPA) axis genetic variation is associated with pain risk. This study aims to explore possible effects of prolonged childhood separation from parents and HPA polygenic risk score (PRS) on pain among adolescents in rural China. METHOD: We used data from 219 adolescents in rural area of Fuyang city, Anhui province, China. Parent-child separation was collected through interview and pain intensity was reported using the 11-point Numerical Rating Scale. SNP genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique. The PRS was computed based on 3 single nucleotide polymorphisms (SNPs) in 2 genes (FKBP5 and NR3C1) related to HPA-axis stress reactivity. RESULTS: Pain among adolescents separated from both parents scored higher compared to those without parent-child separation, however, this association was only observed in adolescents with moderate to high tertiles of PRS groups (parent-child separation in moderate group vs. no parent-child separation in moderate group 3.07 vs. 1.57, P < 0.001; parent-child separation in highest group vs. no parent-child separation in highest group 3.02 vs. 1.26, P < 0.001; parent-child separation in lowest group vs. no parent-child separation in lowest group 2.34 vs. 1.25, P = 0.225). After controlled for demographic characteristics, psychopathological symptoms, adverse childhood experiences, parental warmth, prolonged childhood parent-child separation increased pain scores by 1.52 points (95% CI0.72, 2.33) and 1.72 points (95% CI1.13, 2.31) in moderate and high PRS groups, respectively. CONCLUSION: Our findings suggest that adolescents separated from both parents while carrying more risk alleles related to HPA-axis stress reactivity are at heightened risk of pain.