Physiological Stress Reactivity in Childhood Leukemia and Lymphoma Patients and an Exploration of Neurological and Behavioural Characteristics Associated with Stress Regulation

Significant stress during childhood is associated with health and functional consequences related to dysfunctional physiological stress regulation. Childhood cancer is a stressful experience with indirect evidence of altered regulation of the many systems integrated for appropriate stress regulation. No studies have investigated stress reactivity in this population, however evidence of altered i) physiological stress signalling, ii) neurological structure and function, and iii) coping characteristics, including physical activity and fitness, and psychosocial function, have been reported. To investigate this, 15 childhood cancer patients ages 8-18 who had completed treatment in the previous 6-36 months, and 16 age and sex matched healthy controls were recruited to participate in the study. Participants completed psychological stress testing (TSST- C), resting structural brain scans (DTI), a submaximal aerobic test, in-magnet exercise using 31P MRS, as well as questionnaires relating to physical activity habits, psychological resilience, quality of life, and stress experiences. Salivary samples for cortisol, sAA, and cytokines, as well as, HR, and ratings of perceived stress were collected at 3 time-points prior to (home, -15 minutes, -0 minutes) and 3 time-points following (+0 minutes, +15 minutes, +45 minutes) the TSST-C. No group or interaction effects were observed for HPA reactivity, but patients exhibited lower sAA and HR responses, as well as higher overall IL-8 and TNFa concentrations. Resting DTI showed significant differences between groups for mean FA, MD, RD, and AD of corticolimbic regions analysed. Regional FA differences were also found in the bilateral amygdalae, hippocampi, and interhemispheric limbic lobe. Lower estimated relative VO2peak and HR responses to exercise, as well as ATP regeneration by oxidative phosphorylation and anaerobic glycolysis, and physical activity were found in the patient group, with moderate to large effect sizes. No significant differences were found between groups for psychological wellbeing. These findings indicate that childhood leukemia and lymphoma patients have evidence of blunted SAM reactivity to psychological stress, and neurological and behavioural characteristics that may increase their risk of stress dysregulation and associated adverse health and functional outcomes.Ph.D