medRxiv PreprintsInternational7 October 2026
Neuroplasticity-Based Treatment Prioritization in Major Depressive Disorder: A Two-Cohort Study
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Background: Antidepressant selection in major depressive disorder remains trial-and-error, and no biomarker identifies which drug will work for an individual patient. Because neuroplasticity is a convergent mechanism of antidepressant response, we tested whether it could serve as a drug-specific biomarker in patient-derived neurons. Methods: We developed the Neuroplasticity Score (NPS), integrating structural and synaptic features from high-content imaging of patient-derived cortical neurons, and validated it against graded brain-derived neurotrophic factor (BDNF) exposure in neurons from 16 h
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