Molecular reflection of the mind: Exosomes in major depressive disorder

Exosomes, nanoscale extracellular vesicles (EVs) released by neural and peripheral cells, have become essential mediators in major depressive disorder (MDD). Their diverse cargo, including MicroRNAs (miRNAs), proteins, lipids, and metabolites, impacts key biological processes involved in depression, such as neuroinflammation, synaptic plasticity, hypothalamic-pituitary-adrenal (HPA) axis activity, and mitochondrial function. Therapeutically, both natural and engineered exosomes are being researched for their ability to deliver neuroprotective and anti-inflammatory molecules across the blood-brain barrier (BBB). In this review, we carefully analyze current findings, highlighting advantages and drawbacks across different cohorts, and identify common limitations that hinder reproducibility. We also suggest a framework connecting mechanistic insights with biomarker discovery and therapeutic development. Overall, these advances underscore exosomes as versatile tools for precision psychiatry.