Subjective insomnia symptoms and sleep duration are not related to hypothalamic–pituitary–adrenal axis activity in older adults
Symptoms of insomnia are common in late life, with prevalences in non‐institutionalized older adults ranging from 20 to almost 50% (Ohayon, 2002; Ohayon and Reynolds, 2009). Disturbances in sleep have a major impact on quality of life and increase the risk of falls (Stone et al., 2014), substance use and physical and mental health problems, such as depression (Foley et al., 2004). It has been suggested that sleep disturbances might be associated with dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis (Buckley and Schatzberg, 2005). A cascade of processes in the HPA axis results in the excretion of cortisol in a diurnal rhythm, with a post‐awakening increase (Elder et al., 2014; Pruessner et al., 1997) followed by a decline throughout the day, reaching the lowest point during the first half of the nightly sleep period and rising again until the morning (Weitzman et al., 1971). To measure the negative feedback loop of the HPA axis, the dexamethasone suppression test (DST) was developed (APA, 1987) initially to diagnose Cushing's disease. The DST has also been proposed as a biomarker of psychiatric diseases such as depression (American Psychiatric Association, 1987). Dexamethasone suppresses the nocturnal production of adrenocorticotrophic hormone (ACTH), resulting in low cortisol levels the next morning (Buckley and Schatzberg, 2005). However, research outcomes on the association between cortisol levels and sleep duration and insomnia symptoms are not consistent. In a population‐based study (mean age 61 ± 6 years), self‐reported short sleep duration and symptoms of insomnia were associated with a flatter diurnal slope in cortisol secretion due to raised evening cortisol (Kumari et al., 2009), and short sleep duration was associated with an increased cortisol awakening response. Another study found no association between awakening cortisol and sleep duration or quality in middle‐aged adults (Zhang et al., 2011). A recent population‐based study in middle‐aged adults found an association between poor subjective sleep quality and enhanced negative feedback of the HPA axis after the intake of 0.25 mg dexamethasone the night before (Luik et al., 2015).
Insomnia symptoms are reported in 40–90% of patients with depression (Tsuno et al., 2005). Previous studies in depressed older adults showed that depression is associated with both increased and decreased basal cortisol levels (Bremmer et al., 2007; Penninx et al., 2007), higher evening cortisol in a normal circadian cortisol pattern (Balardin et al., 2011) and a higher awakening response, and a flatter morning curve (Rhebergen et al., 2015). It has been suggested that depression results in hyperactivity of the HPA axis, which inhibits sleep and increases awakenings (Arborelius et al., 1999). Conversely, fragmented sleep might exacerbate HPA axis dysfunction which, in turn, may worsen sleep (Buckley and Schatzberg, 2005).
Previous studies have shown that changes in some cortisol parameters were related to age (Veldhuis et al., 2013), as well as the occurrence of symptoms of insomnia (Ohayon, 2002; Ohayon and Reynolds, 2009). However, it is not known whether the influence of HPA axis activity on sleep also changes with age. Therefore, the present study measured the association between HPA axis activity and insomnia symptoms in a large cohort of both depressed and non‐depressed participants of the Netherlands Study of Depression in Older persons (NESDO). We hypothesized that insomnia symptoms and shorter sleep duration are associated with an increased cortisol awakening response and evening cortisol levels, and that these relationships are stronger in depressed older than in non‐depressed older adults.