to lithium, a commonly used pharmacotherapy for BD, revealed lower threshold for action potentials and higher firing frequencies for BD neurons (Mertens et al., 2015b). Interestingly, BD neurons from lithium responders displayed a reduction in hyperexcitability following lithium treatment, in contrast to non-responder neurons (Mertens et al., 2015b). RNAseq analyses showed a partial normalization of mitochondrial gene levels in the lithium responder group (Mertens et al., 2015b). A subsequent hiPSC study of dentate gyrus-like neurons from BD patients confirmed hyperexcitability of BD neurons and differential reductions in hyperexcitability following lithium treatment (Stern et al., 2017). Furthermore, differences in spiking shape were analyzed revealing that lithium responders had a larger sodium current than controls, whereas non responders had smaller sodium currents (Stern et al., 2017). These studies illustrate how selected hiPSC-derived neurons can respond to appropriate medications and predict patient response, which is notoriously variable in concordance with disorder heterogeneity (Drozda et al., 2014).
