Die Neuroendokrinologie von Stress und die Pathophysiologie und Therapie von Depression und Angst

Zusammenfassung

Präklinische, aber auch insbesondere klinische Studien der vergangenen Jahre haben gezeigt, dass bestimmte Veränderungen des Stresshormonsystems eine wichtige Rolle in der Pathophysiologie und Therapie von Depression,Panikstörung und posttraumatischer Belastungsstörung spielen. Das Stresshormonsystem,die Rolle des Corticotropin-releasing-Hormons, von Kortikosteroiden und ihren Rezeptoren, ebenso wie die Rolle natriuretischer Peptide und neuroaktiver Steroide werden im Folgenden dargestellt.

Antidepressiva sind derzeit Mittel der 1.Wahl in der Psychopharmakotherapie depressiver Störungen, wie auch von Angsterkrankungen, und haben bemerkenswerte Effekte auf das Stresshormonsystem.Die Normalisierung des Stresshormonsystems ist ein wichtiger Prädiktor für den weiteren klinischen Verlauf.Der therapeutischen Beeinflussung des Stresshormonsystems könnte eine wichtige Rolle in der Psychopharmakotherapie von Depression und Angststörungen zukommen.

Summary

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder.The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described.We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment.Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested.Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks.Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders.Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF.This dissociation is probably related to an increased risk of this disorder.We further review recent data that describe an important role of GABA_A-receptor modulatory,3α-reduced neuroactive steroids in major depression, anxiety, and its treatment.Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors.Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder.Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.