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Schizophrenia spectrum disorder (SSD) is a common mental disorder causing severe and chronic disability. Epigenetic changes in genes related to the hypothalamic–pituitary–adrenal (HPA) axis are believed to play an important role in SSD pathogenesis. The methylation status of the corticotropin-releasing hormone ( CRH ) gene, which is central to the HPA axis, has not been investigated in patients with SSD. We investigated the methylation status of the coding region of the  CRH  gene (hereafter,  CRH  methylation) using peripheral blood samples from patients with SSD. We used sodium bisulphite and MethylTarget to determine  CRH  methylation after collecting peripheral blood samples from 70 patients with SSD who had positive symptoms and 68 healthy controls. CRH  methylation was significantly increased in patients with SSD, especially in male patients. Differences in  CRH  methylation were detectable in the peripheral blood of patients with SSD. Epigenetic abnormalities in the  CRH  gene were closely related to positive symptoms of SSD, suggesting that epigenetic processes may mediate the pathophysiology of SSD.

Sex-dependent association of DNA methylation in the coding region of the corticotropin-releasing hormone gene and schizophrenia spectrum disorder