SCZD hiPSC neurons from heterogeneous patients had similar deficits, replicating some but not all aspects of the cellular and molecular phenotypes observed in post-mortem human studies and animal models (SI Table 1). We observed decreased neuronal connectivity in SCZD hiPSC neurons, but not defects in synaptic function; this may reflect technical limitations of our synaptic activity assays. Due to the heterogeneity of our patient cohort and small sample size, our findings might not generalize to all subtypes of SCZD and our microarray comparisons of SCZD and control hiPSC neurons are necessarily preliminary. Gene expression studies of hiPSC neurons permit straightforward comparisons of antipsychotic treatments on live, genetically identical neurons from patients with known clinical treatment outcomes, eliminating many confounding variables of postmortem analysis such as treatment history, drug or alcohol abuse, and cause of death. For example, though Loxapine is characterized as a high affinity antagonist of serotonin 5-HT2 receptors and dopamine D1, D2 and D4 receptors22, treatment of SCZD hiPSC neurons resulted in altered gene expression and increased neuronal connectivity.
