LAUSR

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 6878 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.