recent study using an iPS cell model for human BD reported the cellular phenotypes of hippocampal dentate-gyrus like human neuronal cells from manic type I BD patient fibroblasts (Mertens, Wang, et al., 2015). Electrophysiology and Ca2+ imaging revealed hyperactive action potential firing in BD derived neuronal cells compared to that of controls, which was attenuated with lithium administration. Intriguingly, a decrease in action potential bursting was only observed in human neuronal cells derived from patients who also responded to lithium treatment clinically. This study indicates that neuronal hyperactivity is a BD phenotype, and the BD model created is directly linked with the manic clinical symptoms seen in patients with BD. Mechanistically, the lithium mediated reduction in neuronal hyperexcitability can be explained by alterations in gene expression; specifically, 560 genes were differentially affected in lithium responsive neurons compared to only 40 genes variably expressed in neurons that had no response to lithium application. This study (Mertens, Wang, et al., 2015) provided us with a unique example of disease relevant phenotypes isolated in the dish that are directly translatable to the clinic. Furthermore, this study gives direct evidence that cohorts of patients exhibiting similar clinical phenotypes may exhibit differential response to therapeutics
