Cortisol is a neurohormone released after a cascade response to stressors that begins in the hypothalamus, moves to the pituitary gland, and then to the adrenals, which secrete cortisol into the bloodstream as the final stage in this cascade. Cortisol affects many physiological functions, including vital anti‐inflammatory and immunosuppressive actions, as well as metabolism and homeostasis. Consequently, a basal concentration of cortisol is required at all times but may become immediately elevated in response to physical or mental stressors, usually returning to basal levels later. Underneath this immediate response to stressors, cortisol displays a diurnal variation so that concentrations are at their apex about 45 min after waking in the morning and decrease to their nadir in the early evening, a process referred to as the diurnal fluctuation in cortisol. However, this variation may become dysregulated by chronic stress and instead become consistently elevated, resulting in hypercortisolemia, which is characterized by an ongoing elevated concentration of cortisol in the bloodstream that is associated with pain, fatigue, increased risk of heart disease, and the symptoms of anxiety, muscle wastage, and hyperglycemia.

The comparative strength of the 5-HTTLPR polymorphism as a 'predictor' of depression after major stress, versus the 'protective' effect of psychological resilience (PR) against depression after major stress, was tested in a homogeneous sample of older men who had all received a diagnosis and treatment for prostate cancer. Results supported the association between PR and lower depression after stress, but did not support the association between the 5-HTTLPR and elevated depression after stress. Examination of PR at scale, factor, and item level identified the specific PR-related behaviour that was the most powerful predictor of low depression. These data suggest that the carriage of the short form of the 5-HTTLPR may negate the protective effect of PR against depression in these men, or that PR may nullify the depression vulnerability of this form of the 5-HTTLPR. These findings may explain some of the 'null' findings regarding the link between the 5-HTTLPR and depression in the wider literature by arguing for an interaction between these two factors in the association between major stress and depression.

Objective: To investigate the effect of chronic stress as measured in cortisol concentrations upon the association between psychological resilience (PR) and depression in prostate cancer (PCa) patients. Methods: A total of 104 men with PCa completed inventories on PR, depression, and background factors, plus gave a sample of their saliva for cortisol assay. Results: The inverse correlation between PR and depression was present only for PCa patients with low or moderate concentrations of salivary cortisol (when classified as more than 1.0 SD below the mean vs within 1.0 SD of the group mean) but not for those men whose cortisol was >1.0 SD from the group mean. Specific PR factors and behaviours that made the greatest contribution to depression were identified for the low and moderate cortisol groups. Conclusions: These results suggest that there are particular aspects of PR that are most strongly related to depression, but that PR's inverse association with depression may be absent in participants with extreme chronic physiological stress.