Psychosocial Mediators of the Fatigue–Pain Relationship in Adolescents with Sickle Cell Disease
Ryan N James, Kathryn Russell, Jerlym S PorterAbstract
Background
Adolescents with sickle cell disease (SCD) often experience significant fatigue, which can exacerbate pain and impair daily functioning. However, the psychosocial mechanisms linking fatigue and pain remain understudied. Identifying these mechanisms is critical for developing interventions that target both physical symptoms and psychosocial contributors of pain. As such, this study examined whether depression symptoms, social stress, and family functioning mediate the relationship between fatigue and pain outcomes in youth with SCD.
Methods
The study included 119 adolescents with sickle cell disease (age range: 12–17 years, mean age = 15.0), of whom 51% were male. Participants had the following SCD genotypes: 60.5% HbSS, 21.8% HbSC, 10.1% HbSβ+, and 7.6% HbSβ⁰. They were recruited from a pediatric hematology clinic and completed validated self-report measures of fatigue (PedsQL Multidimensional Fatigue Scale), pain severity and impact (PedsQL SCD Module – Pain and Hurt and Pain Impact scales), depression symptoms and social stress (BASC-3), and family functioning (McMaster Family Assessment Device – General Functioning scale). Regression-based mediation analyses were conducted to examine whether depression symptoms, social stress, and family functioning mediated the relationship between fatigue and pain outcomes, controlling for age, sex, and SCD genotype.
Results
Greater fatigue was significantly associated with higher pain severity and pain impact. Depression symptoms (z = 2.20, p = .028) and social stress (z = 2.16, p = .031) fully mediated the association between fatigue and pain severity, suggesting that these psychosocial factors may contribute to the observed relationship between fatigue and pain severity. Family functioning partially mediated the relationship between fatigue and pain impact (z = 1.69, p = .091), suggesting that supportive family dynamics may buffer the functional consequences of fatigue-related pain. These results highlight distinct psychosocial processes associated with the relationships between fatigue, pain intensity, and pain impact in adolescents with SCD.
Conclusions
These findings suggest that fatigue may influence pain outcomes in adolescents with SCD through distinct psychosocial mechanisms, including depression symptoms, social stress, and family functioning. Interventions targeting these psychosocial factors may reduce fatigue-related pain and support daily functioning. However, due to the cross-sectional nature of the study, conclusions about causality cannot be drawn. Additionally, the restricted age range limits generalizability, and future research should include older adolescents and young adults, particularly during the transition to adult care when SCD-related complications and disease burden often increase. Expanding the age range and using longitudinal designs will be important for clarifying causal pathways and informing developmentally tailored, comprehensive symptom management strategies.