The most highly up-regulated protein-coding gene is tachykinin receptor 3 (TACR3, NK3 receptor, 1.24-fold, Fig. 5D). NK3 antagonists have been tested in SCZ and other CNS diseases42. Moreover, rat and human studies have suggested a role for the NK3 receptor in memory and cognition43, both key impairments of schizophrenia. Insulin-like growth factor 2 (IGF2), the most strongly down-regulated gene (1.33-fold, Fig. 5D), can rescue neurogenesis and cognitive deficits in certain mouse models of schizophrenia44. Also included among the top 100 differentially expressed genes are the alpha 5 subunit of the GABA A receptor (GABRA5) and calbindin (CALB1), genes previously reported as differentially expressed in cortical tissue from schizophrenia patients, suggesting GABAergic interneuron dysfunction45. Available in situ hybridization data from DLPFC suggest that genes identified by DE analysis display various degrees of cell-type specificity, which could affect the estimated fold changes (Supplementary Fig. 10).
