Kristen Brennand, from the Icahn School of Medicine at Mount Sinai, spoke about the inherent value of modeling predisposition, rather than end-stage disease, in the context of schizophrenia (SZ), noting that gene expression patterns characteristic of SZ hiPSC neurons (Brennand et al., 2011) are conserved in SZ-hiPSC-derived NPCs (Brennand et al., 2015). She presented several phenotypical readouts that would be predictive for SZ predisposition in vitro, such as migration defects (Brennand et al., 2015), WNT signaling defects (Topol et al., 2015), and perturbations in neuronal connectivity (Brennand et al., 2011) and activity (Yu et al., 2014). By studying the disease phenotype in vitro, she also gained some insight on the disease biology; through the analysis of global expression profiles from SZ-derived NPCs, she reported differential expression of genes and microRNAs related to the migration changes observed in vitro. Additionally, Brennand is working with patient families and a cohort of childhood-onset SZ patients to correlate SZ-related genetic mutations with gene expression levels.
