Major Depressive Disorder (MDD)

Brain-Derived Extracellular Vesicles for Analysis of Treatment Resistant Major Depressive Disorder

Progress in developing diagnostics and therapeutics for psychiatric conditions has lagged far behind other medical specialties. While this is due, at least in part, to the complexity of the brain, it primarily stems from an inability to access and assess the biochemistry of brain cells. Developing noninvasive methods for sampling brain cells would fundamentally transform our ability to diagnose and treat psychiatric conditions. Our strategy for noninvasively sampling brain cell contents involves utilizing brain-derived extracellular vesicles (EVs) from biofluids such as cerebrospinal fluid and plasma.

This project aims to 1) identify cell-type specific targets using gene expression analysis for astrocytes, microglia, oligodendrocytes, and neurons, and analytically validate Simoa assays to potential immunocapture targets and assess their EV associations; 2) Validate pulldown for each viable EV-associated immunocapture target and show that the EV contents are specific to a given brain cell-type using proteins and mRNAs unique to that cell type; 3) Measure specific proteins, metabolites, and mRNAs of interest in brain-derived EVs from patients with MDD who are treatment responsive, treatment non-responsive, as well as from healthy controls with no personal or family history of MDD.

Funding: Multi-year Wellcome LEAP Multi-Channel Psych grant