We tested the ability of the clinical antipsychotics to rescue SZ neurosphere migration: treatment with neither loxapine nor clozapine improved aberrant migration of SZ neurospheres (463 total SZ neurospheres were analyzed relative to 428 total control neurospheres). Clozapine had no significant effect on SZ neurosphere migration in this assay (Supplementary Figure 6F). Forty-eight-hour loxapine treatment reduced migration of control (P<0.007) and SZ neurospheres (P<0.02), an effect that was substantially exaggerated following 7 days of loxapine treatment (P<0.0001; Supplementary Figures 6F and G). This loxapine-induced reduced neurosphere migration cannot be attributed to decreased cellular replication of NPCs, as assayed immunohistochemically by staining for the cell cycle marker Ki67 (Supplementary Figure 6H). Nanostring gene expression comparisons of loxapine-treated and loxapine-untreated NPCs found decreased expression of many neuronal adhesion genes, particularly NCAM1, NRG3, NLGN1 and NLGN2, following 7 days of loxapine treatment (Supplementary Figure 6J).
