Prospective Biopsychosocial Impacts of Stress and Disease Stigma Among Adolescents and Young Adults with Sickle Cell Disease
Authors: Prussien Kemar V. , Crosby Lori E. , Burke Margaret Mary , Grobes Nikhil D. , Smith Madison N. , Wright Rosalind J. , Thompson Alexis , Schwartz Lisa A. 
Published: December 2024

Introduction: Adolescents and young adults (AYA) with sickle cell disease (SCD) experience a significant increase in psychosocial and biological morbidities during the transition from pediatric to adult-oriented care. Stigma-related stressors experienced during the transition of care could impact long-term morbidities. However, despite the strong literature on the impact of stress and stigma on health outcomes among Black AYA, this research has yet to be applied to individuals with SCD during this critical developmental period. Furthermore, cortisol, a glucocorticoid hormone involved in the regulation of the stress response system, could play a key role in the relation between stress and health outcomes. The purpose of this study was to (a) investigate how stress and disease stigma impact AYA with SCD on psychosocial and biological levels and to (b) explore salivary cortisol as an effect modifier of these associations.
Method: AYA with SCD, aged 16 to 25 years, participated in a 3-month, pilot prospective survey study. Baseline stressors were assessed using the Perceived Stress Scale and Measure of Sickle Cell Stigma. Psychosocial outcomes, including anxiety, depression, and pain interference, were measured using the PROMIS 25 and 29 within a 3-month follow-up survey. Additionally, electronic health record reviews were conducted to identify biological morbidities during the 6 months following baseline. Morbidities were quantified using a cumulative complications variable, guided by the methodology described in Blinder et al. (2013), that encompassed pulmonary, cardiac, renal, infectious, and neurological complications. Pulmonary complications (e.g., acute chest syndrome etc.) were also individually investigated, as they are the leading cause of death in SCD. Finally, participants had the option to engage in a 1-day, at-home, saliva collection between baseline and 3-month follow-up, and the cortisol awakening response was calculated for participants who completed collection.
Bivariate Pearson correlations were employed to assess the relations among continuous variables, and independent samples T-tests were used to examine differences across dichotomous variables (i.e., presence or absence of pulmonary complications). Finally, multivariate linear and logistic regressions determined unique associations when controlling for participant age and gender.
Results: Forty-nine AYA (Meanage = 19.6, 40.8% female sex) completed baseline surveys, 44 AYA completed 3-month follow-up surveys, and 33 participants completed the at-home saliva collection. Cumulative number of complications during the 6 months after baseline ranged from 0 to 2, with pulmonary complications having the most common occurrence among AYA (22.4%).
Bivariate correlations showed that perceived stress predicted psychosocial outcomes, such that stress at baseline was positively correlated with depressive symptoms (r = .55, p &lt; .001) and pain interference (r = .30, p = .045) 3 months later. Disease stigma at baseline was correlated with greater total complications (r = .37, p = .008) and pulmonary complications (t = 3.15, p = .003) during the 6 months after baseline. Further, psychosocial factors at 3-month follow-up were also correlated with health outcomes during the 6 months after baseline. Depression was related to total complications (r = .52, p = .002), and pain interference was correlated with pulmonary complications (t = -2.75, p = .009). All bivariate associations remained significant when controlling for age and gender within multivariate regressions. Neither stress nor stigma were associated with anxiety; however, the relation between stigma at baseline and anxiety approached significance (r = .29, p = .056). Finally, exploratory analyses suggest that cortisol modifies the association between baseline stress and depressive symptoms at 3 months, such that there is a stronger association for AYA with a blunted cortisol awakening response.
Conclusion: Findings from this pilot study imply that perceived stress was prospectively related to psychosocial outcomes, whereas disease stigma predicted biological health outcomes. Additional research is needed to understand the biopsychosocial mechanisms underlying these relations, as this could inform the development of multilevel interventions to reduce the impact of stress and stigma on health outcomes for AYA with SCD during transition of care.