The introduction of induced pluripotent stem cell (iPSC) technology has greatly enabled the advancement of research of psychiatric disorders, making the modeling of human disease possible. Using patch-clamp recordings and somatic calcium imaging, we reported recently42 that hippocampal dentate gyrus (DG) granule-cell-like neurons that were differentiated from fibroblast-derived iPSCs were hyperexcitable. The results were significant but the size and representativeness of the patient cohort were limited.43 We therefore undertook the task of replicating this observation in a separate cohort of patients and using a different somatic cell type to generate iPSCs. Our results demonstrate that immortalized B-lymphocytes44,45 can be reprogrammed to iPSCs and then can be induced to DG-like neurons; the DG granule-cell hippocampal neurons differentiated from BD patients in this new cohort are hyperexcitable. We further show that BD neurons can be divided into two subgroups, each with very distinct and different electrophysiological features depending on their responsiveness to Li. Training a Naïve Bayes (NB) classifier on the electrophysiological features of known patients can successfully predict the responsiveness of an unknown patient to Li. The electrophysiological feature that is
