The predictive value of cortisol levels on 2-year course of depression in older persons

Highlights

• Studies on the association between cortisol and course of depression in older persons are lacking.

• In a cohort of currently depressed older persons, we studied the course of illness.

• As hypothesized, lower cortisol levels predicted unfavorable 2-year course.

• In depressed older persons, evening cortisol levels may serve as a marker to identify persons at risk for unfavorable course trajectories.

Abstract

Background

Depressive disorders in older persons are associated with an altered functioning of the Hypothalamic–Pituitary–Adrenal (HPA)-axis. In adults, a lower cortisol awakening response is a predictor of a worse prognosis of depression, but to date longitudinal studies in older depressed persons are lacking. We hypothesised that a lower cortisol awakening response is also associated with poorer course of depression in later life.

Methods

Data were derived from the Netherlands Study of Depression in Older Persons (NESDO). Participants with a 6-month Major Depressive Disorder (MDD), who provided 2-year follow-up data, were included (n = 246). Logistic regression analyses were conducted to examine the association between diurnal cortisol levels and depressive status at 2-year follow-up.

Results

Both lower (OR = 3.54; 95% CI = 1.59–7.89) and higher evening cortisol levels (OR = 2.41; 95% CI = 1.09–5.35) at baseline were associated with poorer prognosis of MDD. Low dexamethasone suppression was associated with poorer course (OR = 2.37; 95% CI = 1.09–5.16), but failed to reach significance after additional adjustment for severity and chronicity of MDD (OR = 1.98; 95% CI = 0.89–4.42). Cortisol awakening response was not significantly associated with course. Since smoking has a great impact on cortisol levels, we conducted post-hoc analyses including non-smokers only, indicating that lower evening cortisol levels (OR =  2.83, 95% CI = 1.31–6.13) predicted unfavourable course.

Conclusions

This first longitudinal study on cortisol and prognosis of depression in older persons demonstrates that in particular lower evening cortisol levels may predict poorer course in MDD. This finding may have clinical implications. Evening cortisol values may serve as a marker to identify persons at risk for an unfavourable course.

Introduction

Late-life major depressive disorder (MDD) is a debilitating disease, with prevalence rates varying between 0.9% to 9.4% among older community-dwelling persons, and up to 42% among persons living in institutions (Djernes, 2006). Furthermore, about ten percent of the persons in this age group are suffering from minor depression (Beekman et al., 1999). The prognosis of late-life depression is poor as compared to depressions among younger adults. It was demonstrated that chronicity or recurrence of depression affects one-third of depressed older adults (Cole, 1999). Comijs et al. (2015) have recently shown an even more unfavourable prognosis in a large cohort of depressed elderly. They demonstrated that almost half (48.4%) of the depressed persons in this cohort were still suffering from depression at 2-year follow-up. Early onset of depression, higher severity, co-morbid dysthymia and/or physical chronic diseases alongside older age were identified as predictors of poorer course (Beekman et al., 2001, Comijs et al., 2015, Licht-Strunk et al., 2007). In addition to clinical predictors, previous research aimed to disentangle the pathophysiological processes involved in depression and their contribution to the course of depression.

Since decades, the central role of the Hypothalamic–Pituitary–Adrenal (HPA)-axis in the pathogenesis of depression was acknowledged (e.g. Gibbons and McHugh, 1962). However, the majority of studies on cortisol and depression in older persons had a cross-sectional design, limiting insight into the association between HPA-axis functioning and course trajectories of depressive disorders. Some studies focused on the association between cortisol and the onset of depression or depressive symptoms later in life (e.g. Nabeta et al., 2014, Chinthapalli, 2014, Geoffroy et al., 2013), however studies on the predictive value of HPA-axis functioning on the course of current depressive disorders in older persons are lacking. Likewise, the majority of studies on adults examine the impact of HPA-axis functioning on either onset or recurrence of depression (Bockting et al., 2012, Lok et al., 2012, Hardeveld et al., 2015, Dedovic and Ngiam, 2015, Vrshek-Schallhorn et al., 2013). One study examined the association between cortisol and course trajectories of both depression and anxiety disorders in an adult population (aged 18–65 years). It demonstrated that a lower cortisol awakening response was associated with an unfavourable course of illness (Vreeburg et al., 2013). Finally, it has been suggested that an impaired signaling pathway via corticosteroid-activated mineralocorticoid and glucocorticoid receptors would lead to an impaired negative feedback regulation of the HPA system. This could cause high levels of cortisol, which in turn may be associated with unfavorable course of depression (Schüle et al., 2009). Hence, the Dexamethasone Suppression test (DST) was propagated as a putative predictor for course of depressive disorders (e.g. Schweitzer et al., 1987, Charles et al., 1989). However, since then, results from research on its predictive value were inconclusive, and research among older persons is lacking.

Although Bremmer et al. (2007) and Penninx et al. (2007) demonstrated a U-shaped association with both lower cortisol levels and higher cortisol levels being associated with depression in a cross-sectional population based study, a recent meta-analysis (Belvederi Murri et al., 2014) and our own findings (Rhebergen et al., 2015) could not replicate this. Nevertheless, when studying the predictive value of cortisol on the course of depression in older persons, one needs to take a possible U-shape into account, since neglect of this non-linear association may potentially mask underlying associations.

The Netherlands Study of Depression in Older Persons (NESDO) gives us the opportunity to investigate the association between cortisol and longitudinal course of late-life depressive disorders. The aim of this study is to examine the predictive value of cortisol on the 2-year course of depression in older persons, aged 60–93 years. To address the issue of a putative non-linear association, cortisol measures will be divided into tertiles, including lower, average or higher cortisol levels. We hypothesize that lower cortisol levels, a lower awakening response and lower Dexamethasone Suppression ratio may predict an unfavourable course trajectory of depressive disorders in older persons, as compared to average or higher cortisol levels or Dexamethasone Suppression ratio.