Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models
Andrea Perrottelli, Francesco Flavio Marzocchi, Edoardo Caporusso, Giulia Maria Giordano, Luigi Giuliani, Antonio Melillo, Pasquale Pezzella, Paola Bucci, Armida Mucci, Silvana Galderisi
Abstract
The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. In this review, we summarize the results of iPSC-based research on schizophrenia and bipolar disorder, showing disturbances in neurodevelopmental processes, imbalance in glutamatergic-GABAergic transmission and neuromorphological alterations. The limitations of the reviewed literature are also highlighted, particularly the methodological heterogeneity of the studies, the limited number of studies developing iPSC models of both diseases simultaneously, and the lack of in-depth clinical characterization of the included samples. Further studies are needed to advance knowledge on the common and disease-specific pathophysiological features of schizophrenia and bipolar disorder and to promote the development of new treatment options.