BPD affects about 1% of the U.S. population.60 Patients with BPD present with episodes of major depression interspersed with bouts of mania or hypomania. First-line treatment includes mood stabilizers, such as lithium and valproic acid. Over the past 2 years, a few groups managed to generate iPSC-derived neurons from fibroblasts isolated from patients with BPD and healthy control patients.61, 62, 63, 64 In one study, iPSC lines were derived from two brothers with BPD and their unaffected parents.62 Several genes were differentially expressed in BPD-derived neuronal precursor cells, most of which regulate neuronal differentiation, projection and calcium binding. Interestingly, neuronal precursor cells generated from BPD patients showed impaired neural differentiation and decreased proliferation, both of which were rescued by treatment with a selective inhibitor of the enzyme GSK3β (a known target of lithium therapy).62 Another group reprogrammed fibroblasts derived from patients with BPD, half of whom were responsive to lithium treatment, to iPSC-derived hippocampal dentate gyrus granule cell-like neurons, which are reportedly affected in BPD.63 Of note, BPD-derived neurons showed altered expression of mitochondrial, calcium-signaling and neuronal excitability genes. In
