Perceived stress, depressive symptoms, and cortisol-to-cortisone ratio in spot urine in 6878 older adults.

Abstract Background Late life depression and perceived stress could influence disease pathways via reduced 11β-HSD2 activity, particularly given suggestions that reduced 11β-HSD2 activity, which is reflected in the cortisol-to-cortisone ratio, is a risk factor of disease. To date, however, examination of the relationship between the cortisol-to-cortisone ratio and perceived stress or depressive symptoms is insufficient. Methods We examined the cross-sectional association of the cortisol-to-cortisone ratio with perceived stress and depressive symptoms, and analyzed whether cortisol levels modify this association, in 6,878 participants aged 45–74 years. Cortisol and cortisone in spot urine were measured using liquid chromatography-mass spectrometry. Perceived stress during the past year was measured using a self-reported questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Analyses were performed with adjustment for age, sex, lifestyle factors (smoking habit, alcohol consumption, physical activity, and sleeping hours), and physical health factors (body mass index [kg/m2] and medical history [diabetes, hypertension, and medication for hyperlipidemia or corticosteroids]). Results Cortisol-to-cortisone ratio and cortisol were positively associated with perceived stress (% change: 2.33, Ptrend = 0.003; and 4.74, Ptrend = 0.001, respectively), but were not significantly associated with depressive symptoms. Further, the relationship between cortisol-to-cortisone ratio and perceived stress was modified by cortisol level and sex: the positive association between perceived stress and the cortisol-to-cortisone ratio was more evident in subjects with lower cortisol levels (Pinteraction = 0.009) and in men (Pinteraction = 0.026). Conclusions These findings suggest that the cortisol-to-cortisone ratio in spot urine may be a useful marker for non-acute perceived stress in daily life against a possible background of reduced 11β-HSD2 in older adults.