Up until recently, attempts to model neuropsychiatric diseases related to serotonergic transmission in vitro had been unsuccessful. In 2016, two groups independently developed a method for generating serotonergic neurons via transdifferentiation directly from human fibroblasts.43, 44 Of note, Vadodaria and colleagues made use of citalopram, an SSRI, to show that these neurons could be potential tools for screening therapeutic compounds. In contrast, Lu et al.45 used hESCs and fibroblast-derived iPSCs to generate serotonergic neurons via temporal exposure of the cells to growth factors and modulators of signaling pathways. The group subsequently used the SSRI escitalopram to establish the utility of these neurons as screening tools for serotonin modulators. The development of reliable differentiation methods represents a leap forward in dissecting serotonin’s role in depression. If these serotonergic neurons are made from patients, they can be used to screen for new therapeutics and elucidate the unknown mechanisms through which current drugs may function.46, 47 This development may lead to the discovery of new drug targets and new insights into the molecular biology of depression.
