New Molecular Targets for Antidepressant Drugs

• Main Authors: Johannes Kornhuber, Erich Gulbins
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Pharmaceuticals
• Subjects: acid sphingomyelinase; ceramide; sphingomyelin; FIASMA; antidepressant drug; lysosome
• Online Access: https://www.mdpi.com/1424-8247/14/9/894

Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).