<h4>Objectives</h4>This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).<h4>Methods</h4>Seven TRD patients received ESK-IN while continuing oral antidepressants. Here, NEFL is linked to depressive disorder.