Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.
Translational psychiatry November 18, 2025 Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al. 2 citations
In neurons derived from induced pluripotent stem cells of five women with treatment-resistant depression (average age 40.2 years), both the glycoprotein reelin and the ketamine metabolite (2R,6R)-hydroxynorketamine increased expression of several synaptic proteins (GluA1, PSD-95, Dab1, Synapsin I, and p-ERK) within one hour, with effects declining by 24 hours. Gene expression changes were similar for both compounds, though only reelin upregulated mTORC1 signaling. The findings suggest that iPSC-derived neurons may serve as a useful in vitro model for studying treatment-resistant depression and testing potential therapeutics.