Renin-Angiotensin-Aldosterone System: The Forgotten Stress Hormone System: Relationship to Depression and Sleep

Introduction: Neuroendocrine changes in depression have long been recognized, with a focus mainly on hypercortisolism. The other hormone of the hypothalamus-pituitary adrenocortical system, aldosterone, has been widely neglected. Methods: Here we summarize the involvement of the renin-angiotensin-aldosterone system (RAAS) and the regulation of aldosterone in health with a particular focus on sleep-related changes and its role in stress-related conditions, like major depression. Results: We highlight its role in functional systems which could be relevant in the therapy for refractory depression, like inflammatory mechanisms, the monoaminergic and the glutamatergic systems. Furthermore, anatomic areas which specifically mediate the action of aldosterone have been identified. In particular the nucleus of the solitary tract (NTS) seems to have an important role and appears to be a target for antidepressive manipulations, like vagus nerve stimulation. Clinical data demonstrating the efficacy of aldosterone-reducing strategies for specific depressive syndromes are reviewed. Discussion: In particular aspects of differentiation between melancholic vs. atypical depression spectrum disorders are discussed.