Fig. 2: iPSC-derived cortical neurons mimic patient response to an antidepressant.

A Immunofluorescence images and quantifications of the presynaptic marker Synapsin (top panel), postsynaptic marker PSD95 (middle panel), and colocalized markers (bottom panel) in nonresponder untreated (n = 5 patients, n = 52 dendrites), nonresponder bupropion treated (n = 5 patients, n = 54 dendrites), and responder patient iPSC-derived cortical neurons untreated (n = 5 patients, n = 39 dendrites) and treated with bupropion (n = 5 patients, n = 47 dendrites). Scale bars represent 10 µm. B Average dendritic spine length was significantly altered following bupropion treatment only in patient responder-derived cortical neurons, both in average length and in spine length frequency. C Average dendritic spine length in specific spine types. Spine length was significantly changed in patient responder-derived neurons in three out of four spine types. Spine types are illustrated (right panel). D Volcano plot of statistically significant, differentially expressed genes in responder and nonresponder patient-derived cortical neurons following bupropion treatment. Orange line represents FDR < 0.05 (N = 10, n = 5 for each remission group). E Identified biomarker gene expression significantly changed in responder patient-derived cortical neurons following bupropion treatment. One-sided Student’s t test was used for comparisons. *p < 0.05, **p < 0.01, ***p < 0.001. Error bars represent standard error of the mean.