Establishment of a biomarker of peripheral stress in opioid addicts based on the hypothalamic-pituitary-adrenal axis—The improvement effect of exercise

PURPOSE: This study aims to investigate the relationship between peripheral blood oxytocin (OT), vasopressin (AVP), and subjectively perceived stress and cortisol in male opioid addicts based on the hypothalamic-pituitary-adrenal (HPA) axis. We also investigate the impact of exercise on reducing subjectively perceived stress, craving level, negative reinforcement, anxiety, sleep quality, plasma OT, AVP, and cortisol levels. METHODS: Participants were divided into 28 subjects in the low-stress control group (LSC group), 29 subjects in the medium-high stress control group (MTHSC group), and 28 subjects in the moderate-high-stress exercise group (MTHSE group), based on their subjectively perceived stress levels. Subjects in the MTHSE group performed 12 weeks of combined aerobic resistance training (60 min per day, 5 days per week). Plasma OT, AVP, and cortisol concentrations were analyzed via Elisa. PSQI was used to assess the subjective perceived stress, craving, negative reinforcement, anxiety, and sleep quality level, respectively. Mixed-effects ANOVA and Pearson correlation analysis were employed to explore the impact and correlation between different parameters. RESULT: Plasma OT levels significantly increased (95% CI: –7.48, –2.26), while plasma AVP (95% CI: 2.90, 4.10), and cortisol (95% CI: 19.76, 28.17) levels significantly decreased in the MTHSE group after exercise. The PSS (95% CI: 1.756, 4.815), “Desire and Intention” (95% CI: 1.60, 2.71), and “Negative reinforcement” (95% CI: 0.85, 1.90) (DDQ), SAS (95% CI: 17.51, 26.06), and PSQI (95% CI: 1.18, 3.25) scores of the MTHSE group were significantly decreased after exercise. Plasma OT, plasma cortisol, craving, negative reinforcement and anxiety were negatively correlated. Plasma AVP was positively correlated with craving. CONCLUSION: As an auxiliary treatment, exercise improves the plasma OT, AVP, and cortisol levels of opioid addicts, and reduces their subjective perceived stress level, desire, negative reinforcement level, anxiety level, and sleep quality. In addition, peripheral plasma OT, AVP, and cortisol may play a role as potential peripheral biomarkers to predict stress in male opioid addicts.