Abstract
BACKGROUND: Chronic pain (CP) is a debilitating condition characterized by pain lasting longer than three months, significantly impairing physical, emotional, and social functioning. Comorbidities such as depression can exacerbate the severity and persistence of CP, leading to greater functional impairment and diminished quality of life. Characterizing the psycho-socio-behavioural substrates of CP is crucial for improving treatment and prevention strategies based on multidisciplinary approaches. METHODS: The study sample included 750 monozygotic (MZ) and dizygotic (DZ) twin pairs aged 18-82 years, enrolled in the Italian Twin Registry. Non-cancer CP-related characteristics (ie, CP occurrence, intensity and body location) as well as depressive symptomatology, sleep quality and perceived social support were assessed by validated self-report questionnaires. The twin study methodology was applied to control for genetic and shared environmental confounding while estimating the association of CP with psycho-socio-behavioural variables. DATA ANALYSIS: Individual-level and intrapair-level regression were used to estimate the association of CP with psycho-socio-behavioural variables. Biometrical structural equation modelling and mediation analysis were performed to shed light on the etiological mechanisms underlying this association. RESULTS: As regards CP and depressive symptomatology, individual-level association in the total sample of twins and intrapair-level associations in MZ and DZ pairs discordant for CP were all significant and of similar magnitudes, possibly consistent with a quasi-causal relationship. Under the best-fitting biometrical structural equation model, unique environmental factors explained 73% (95% CI: 19-100%) of phenotypic correlation between CP and depressive symptoms. Life satisfaction and sleep quality resulted to mediate the association between CP and depression, with a global indirect effect from CP to depression of 0.32 (0.22-0.44). CONCLUSION: This study provides insights into the relationship of CP with depression, suggesting a quasi-causal connection between them, an important contribution of unique environmental factors in this connection, and a mediating role of sleep quality and subjective wellbeing.