Plasma dehydroepiandrosterone sulphate (DHEAS) and cortisol in patients with mood disorders

Introduction: Preclinical studies suggested that neuroactive steroids may modulate anxiety and depression-related behaviours and may contribute to the therapeutic effects of antidepressant drugs. Several studies have investigated neuroactive steroids concentration during a Major Depressive Episode (MDE). In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Hsiao (2006) found a positive correlation between severe anxiety symptoms and plasma levels of dehydroepiandrosterone sulfate (DHEAS) in 28 medication-free Japanese patients experiencing a MDE. Haren et al. (2007) also found lower serum DHEAS levels associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women. The aim of this study is to replicate these findings in a population of Caucasian medication-free patients during a MDE. Furthermore, we also investigate the correlation between severity of depressive symptoms and the psychopathological profile of patients. Methods: 83 patients (M/F = 43/40 ; mean age 47,70±14,52) with a Mood Disorder during a MDE have been recruited at the Day Clinic of Psychiatry of the Catholic University in Rome. A blood sample for the determination of plasma cortisol and DHEAS levels was collected before antidepressant treatment. Acute symptoms were measured with Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS). Snaith Hamilton Pleasure Scale (SHAPS), Depression Retardation Rating Scale (DRRS) and Aggression Questionnaire (AQ) were used to evaluate the psychopathological features (anhedonia, psychomotor impairment and aggression). Results: No significant correlation between plasma cortisol levels, severity of symptoms and psychopathological features of patients have been observed. DHEAS levels appeared to be negatively correlated to the age of patients (r = -0,54; p = 0,0001). After controlling for age, no significant correlation between DHEAS levels and severity of depression (HDRS scores) has been observed. No correlation has been observed between DHEAS levels and psychopathological features of studied patients (anhedonia, retardation and aggression). A positive correlation, statistically significant, has been found between plasma DHEAS levels and HARS scores (r = 0,43; p = 0,05). Discussion: We replicated the finding of Hsiao who observed plasma DHEAS concentrations positively correlated to HADS anxiety subscale scores, after controlling for age. DHEAS is a neuroactive steroid synthesized both by the brain and adrenal glands related to neurophysiological functions, especially to the cognitive and emotional ones. Some authors have proposed that DHEAS is an anxiety-inducing steroid and also observed some antagonistic activity at GABA-A receptors that can result in more relevant anxiety symptoms. Moreover, according to the hypothesis of a dysregulation of the hypothalamic-pituitary adrenal (HPA) axis in Major Depressive Disorder (MDD), hypercortisolemia and DHEAS, secreted by adrenal glands after ACTH stimulation, could represent further indicators of axis dysregulation. In our sample, DHEAS and cortisol levels did not provide significant correlation to both severity of depression and psychopathological profile. Further studies with more sensitive marker to monitor HPA axis abnormality (e.g. DEX/CRH test), are needed to confirm our results.