Patient iPSC-derived neurons reveal mechanisms underlying antidepressant response: a potential diagnostic tool

Introduction Depression is a leading cause of disability worldwide despite dozens approved antidepressants. There are currently no clear guidelines to assist the physician in their choice drug, with existing tools limited pharmacogenetics that have shown suboptimal response prediction outcomes resulting subscription process largely trial and error one. Consequently, majority depressed patients do not respond first prescribed antidepressant, >30% responding subsequent drugs. We report here on molecular readouts from an vitro-based platform provides patient-specific information antidepressant mechanisms using cortical neurons derived individually each patient. Objectives To assess gene expression differences prefrontal cortex responders non-responders two commonly used antidepressants, selective serotonin reuptake inhibitor Citalopram atypical Bupropion. Methods Patient-derived lymphoblastoid cell lines Sequenced Treatment Alternatives Relieve (STARD) study known or Bupropion were reprogrammed then differentiated neurons. Differential analysis was preformed identify genes differentially expressed between drug non-responders. Results Significant differential 359 (Fig1A) 12 (Fig1B). Clustering showed high agreement both drugs (Fig1). Functional enrichment revealed biologically relevant pathways differ versus Citalopram. Image: Figure 1. Heatmap show significant (A) (B) Color scaled expression; columns samples. Column side colors represent Colum line dendrograms unsupervised hierarchical clustering. Conclusions Gene patterns depression according common antidepressants different groups. The identification distinct dependent can help elucidate underlying activity, supporting new development prediction. Disclosure Interest None Declared