Assessment of Salivary Cortisol and Amylase as Stress Response Biomarkers in Patients with Major Depressive Disorder: the Role of Sex Differences

Abstract The aim of this study was to evaluate gender differences in the stress response of patients with major depressive disorder (MDD) using a moderate cognitive task as a challenge. We assessed 67 MDD patients (38 women) and 38 healthy participants (16 women) aged 18 to 45 years. All subjects were assessed for depression and anxiety symptoms, perceived level of stress, and stressful life events. Saliva samples for cortisol and amylase assessment were collected in the afternoon prior to a ten-minute arithmetic task (t0), immediately after the task (10 min), and at 20, 30, 40 and 60 min. Heart rate variability parameters were calculated from 5-minute recordings before task performance. Autonomic parameters were reduced both in men and women with MDD. A difference in salivary amylase response in healthy control women as compared to women with MDD was demonstrated (F [5, 165] = 3.3; p < 0.01), with a maximal elevation in controls at 20–30 minutes from the start of the arithmetic task. A trend to a cortisol elevation was revealed in control women (F [5, 165] = 2.1, p < 0.06), maximal at 30 min. No significant differences for amylase or cortisol responses were found between male MDD subjects and controls (F [5, 190] = 0.59; p < 0.7 and (F [5, 175] = 0.45, p < 0.8, respectively). Thus, a moderate cognitive stressor such as a timed arithmetic task is able to evoke a response of hypothalamic-pituitary-adrenal and sympathetic adrenergic parameters in healthy females. This stressor, however, may be insufficient for a detectable response in males. Gender-dependent differences in stress reactivity should be accounted for when studying stress response in healthy individuals and patients with mental conditions.