The neurodegenerative hypothesis of depression and the influence of antidepressant medications

Abstract

Depression is a complex neurological disease that holds many theories on its aetiology and pathophysiology. The monoamine strategy of treating depression with medications to increase levels of monoamines in the (extra)synapse, primarily through the inhibition of monoamine transporters, does not always work, as seen in patients that lack a response to multiple anti-depressant exposures, as well as a lack of depressive symptoms in healthy volunteers exposed to monoamine reduction. Depression is increasingly being understood not as a single condition, but as a complex interplay of adaptations in various systems, including inflammatory responses and neurotransmission pathways in the brain. This understanding has led to the development of the neurodegenerative hypothesis of depression. This hypothesis, which is gaining widespread acceptance posits that both oxidative stress and inflammation play significant roles in the pathophysiology of depression. This article is a review of the literature focused on neuroinflammation in depression, as well as summarised studies of anti-inflammatory and antioxidant effects of antidepressants.