In a pioneering study, Brennand et al. 127 constructed the first hiPSC model of Schizophrenia (SCZD). The Brennand et al. study interestingly echoed many of the neuropathological and pharmacological results showing diminished neuronal connectivity, decreased neurite number, decreased PSD95-protein levels, and decreased glutamate receptor expression. However they were also able to build on post-mortem studies in that they revealed further information about the cellular pathway underpinnings of SCZD – namely, their gene expression profiles of SCZD patient derived neurons had abnormal expression of components of the cyclic AMP and WNT signaling pathways 127. The same group later showed that SCZD patient-derived neuronal progenitor cells (NPCs) had aberrant migration, increased oxidative stress, and perturbed responses to environmental stresses 128. A separate study by this group suggests increased protein synthesis due to increased levels of ribosomal and translation initiation and elongation factor proteins in SCZD patient-derived cultures, hinting at yet another possible mechanism of disease 54.
