We identified hypertrophic OPCs as a new histopathological signature of schizophrenic brains in both human patients and mouse model, provided compelling evidence that expression of DISC1 exon 3 splicing variant solely in OPCs is sufficient to suppress synaptogenesis, and presented a potential mechanism by which the onset of schizophrenia related to OPCs could be driven by the overproduction of Wif1, a Wnt-pathway inhibitor, in response to the hyperactivation of Wnt/β-catenin signaling in DISC1-Δ3 OPCs. Here, DISC1 is linked to schizophrenia.