Abstract

ROLE OF NEUROINFLAMMATION IN DEPRESSION AND ANTIDEPRESSANT DRUG DEVELOPMENT: EMERGING INSIGHTS AND THERAPEUTIC PERSPECTIVES

Mr. Suraj S. Chilkawar*, Dhananjay R. Tidke, Dr. Dinesh R. Chaple, Ayush V. Umare, Sumit S. Raut, Deepak S. Dodke

Abstract

As a result of several triggers, depression is a multifactorial psychiatric disorder characterized by constant sadness, anhedonia, and disturbances in cognitive processes. Millions of people worldwide experience this mental illness, with traditional antidepressants targeting mainly monoaminergic mechanisms. Despite this, a considerable number of patients show inadequate responsiveness to existing treatments. Recent studies suggest a connection between depression development and neuroinflammation, with activation of microglia and astrocyte cells along with elevated levels of pro-inflammatory cytokines, such as IL-6, TNF-α, and IL-1β, affecting neurotransmission, neurogenesis, and HPA dysfunction. This review explores the role of neuroinflammation in depression mechanisms and possible applications in developing novel antidepressants. Specific focus will be paid to the most prominent pathways involved in neuroinflammation – proinflammatory cytokines, oxidative stress, and immune imbalance. The article reviews their relationship with neurotransmission mechanisms and provides insights into potential antidepressant therapies involving the reduction of inflammation. The discovery of neuroinflammation involvement in depression paves the way for designing a new generation of antidepressants. Based on immunology, neurobiology, and pharmacology, future studies may help in creating effective and fast-acting drugs for treating depression.

Keywords: Antidepressants, Astrocytes, Cytokines, Depression, HPA axis, IL-1β, IL-6, Immune system, Inflammation, Microglia, Neurogenesis, Neuroinflammation, Neuroplasticity, NMDA receptor, Oxidative stress, SSRIs, TNF-α, Tryptophan metabolism, Kynurenine pathway,