Abstract
ObjectiveAssociations of cortisol and depression vary at different life-stages, yet population-based, prospective studies are scarce. We aimed to assess associations of morning cortisol with depressive symptoms in mid-life taking account of lifetime psychological health.MethodsParticipants were 5,403 men and women from the 1958 British Birth Cohort whose salivary cortisol was assessed at 45y (45min after waking (T1) and 3h later (T2)) and who completed the 5-item Mental-Health Index (MHI-5) about depressive symptoms at age 50y. Lifetime psychological health was identified from child and adult measures.ResultsFor women, higher T2 cortisol at 45y predicted depression (MHI-5 scores ≤52) at 50y (odds ratio [OR]=1.17; 95% confidence intervals [CI] 1.05,1.30 per standard deviation increase in T2 cortisol), attenuating when adjusted for current (45y) and previous (7-42y) psychological health (OR=1.11; 95% CI 0.98, 1.24). Similarly, an association in women of flatter cortisol delta (T2-T1) with depressive symptoms at 50y weakened after adjustment for current (45y) and previous (7-42y) psychological health. For men, lower T2 cortisol at 45y predicted greater depressive symptoms at 50y and the association strengthened when adjusted for lifetime psychological health. Likewise, lower cortisol AUC predicted higher risk of depression for men after adjusting for prior psychological health (OR=0.85; CI 0.72, 1.00). Associations were largely unaltered by control for covariates.ConclusionsIn women, higher cortisol in late morning at 45y is prospectively associated with depressive symptoms at 50y through a link with lifetime psychological health. In men, lower cortisol predicts subsequent symptoms, independent of depressive history.
Highlights
Major depression is the most common mental health illness[1] and a leading contributor to the global burden of disease[2]
T2 cortisol was not associated with depressive symptoms at 50y in models adjusted only for testing conditions, but the association strengthened after taking account of lifetime psychological health (OR=0.85; CI 0.71, 1.02, p=.075 for categorical outcome; β=-0.04, p=.008 for continuous outcome) and remained after controlling for covariates
T2 cortisol levels were lower for incident symptoms versus not depressed (adjusted geometric mean=6.34 vs 7.22 (7.03,7.41), p=.007) but not for remitted or persistent symptoms
Summary
Major depression is the most common mental health illness[1] and a leading contributor to the global burden of disease[2]. In longitudinal studies of children and adolescents, hyperactivity of the HPA (as indicated by higher cortisol awakening response (CAR) and higher morning cortisol) has been shown to predict depression onset and recurrence[6,7,8,9,10,11,12,13]. In 116 initially not-depressed women (but at high risk for mental health difficulties) aged 23-58y, elevated morning cortisol at 8.00h was found to be associated with onset of major depressive episode in a 1y period[14] and, higher levels of cortisol after dexamethasone-CRH test predicted relapse in 74 inpatients remitted from depression[16]. If socio-emotional and HPA-axis development are co-founded early in life and continue to co-evolve, earlier associations should be taken into account in investigations of cortisol and depression at later life stages
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