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 addition, when compared with controls, BPD-derived neurons exhibited a hyperexcitability phenotype as evidenced by higher frequency of spontaneous action potentials. Remarkably, a 1-week treatment with lithium partially normalized changes in mitochondrial gene expression and hyperexcitability phenotype only in neurons derived from patients with BPD who were responsive to lithium.63 These recent findings suggest a role for mitochondrial signaling in BPD and shed light on potential molecular mechanisms that could explain the differences in patient responsiveness to lithium treatment.65
