Differential Stress Reactivity in Children with Sickle Cell Disease

Sickle cell disease (SCD) is a genetic condition characterized by multiple clinical complications, including acute and chronic pain and co-morbid mental health (MH) symptoms. Expression of complications is variable and not easily linked with genotype. Stress reactivity, measured by autonomic nervous system (ANS) and hypothalamic pituitary axis (HPA) responses has been associated with MH symptoms and physical illness for healthy children. Demonstrating a relation between stress reactivity and clinical complications in SCD, including daily pain, could aid in predicting which children will express severe disease and therefore benefit the most from high-risk disease-modifying therapies. We examined ANS (cardiovascular measures) and HPA (salivary cortisol) reactivity to challenging everyday tasks in relation to pain and MH symptoms in a prospective cohort study of children with SCD. Children (Mean age = 8.1 years; 55% Hemoglobin SS disease; 31 girls, 29 boys) reported on their pain coping strategies and daily pain. Parents rated family stress and child MH symptoms. We found significant associations between greater cortisol reactivity and increased MH symptoms; higher resting cortisol and greater daily pain intensity; and increased MH symptoms and frequent daily pain. Increased ANS reactivity predicted poor pain coping, which in turn was associated with greater pain intensity. Our findings suggest that ANS and HPA reactivity may offer complementary approaches for characterizing children vulnerable to expressing severe SCD. Understanding the stress reactivity profile for children with SCD may allow for patient-specific clinical interventions that focus on regulation of biological processes and physiological reactivity.