Epigenetic aging in major depressive disorder: Clocks, mechanisms and therapeutic perspectives

Depression, a chronic mental disorder characterized by persistent sadness, loss of interest, and difficulty in daily tasks, impacts millions globally with varying treatment options. Antidepressants, despite their long half-life and minimal effectiveness, leave half of patients undertreated, highlighting the need for new therapies to enhance well-being. Epigenetics, which studies genetic changes in gene expression or cellular phenotype without altering the underlying Deoxyribonucleic Acid (DNA) sequence, is explored in this article. This article delves into the intricate relationship between epigenetic mechanisms and depression, shedding light on how environmental stressors, early-life adversity, and genetic predispositions shape gene expression patterns associated with depression. We have also discussed Histone Deacetylase (HDAC) inhibitors, which enhance cognitive function and mood regulation in depression. Non-coding RNAs, (ncRNAs) such as Long Non-Coding RNAs (lncRNAs) and micro RNA (miRNAs), are highlighted as potential biomarkers for detecting and monitoring major depressive disorder (MDD). This article also emphasizes the reversible nature of epigenetic modifications and their influence on neuronal growth processes, underscoring the dynamic interplay between genetics, environment, and epigenetics in depression development. It explores the therapeutic potential of targeting epigenetic pathways in treating clinical depression. Additionally, it examines clinical findings related to epigenetic clocks and their role in studying depression and biological aging.