Tabriz Valiasr International Hospital Publication International Journal of Drug Research in Clinics 2980-9835 4 1 2026 01 01 Increased DNA Methylation of the HTR1A Gene Promoter in the Peripheral Blood Mononuclear Cells of Patients with Schizophrenia e9095 e9095 10.34172/ijdrc.9095 EN Zahra Mousavi https://orcid.org/0000-0002-5719-7989 Ali Sadeqzade Oskuyi Hajar Hashemi Sotoubadi Ali Reza Shafiee-Kandjani https://orcid.org/0000-0002-3045-2644 Journal Article 10.34172/ijdrc.9095 2026 01 16 2026 04 29 Introduction: Schizophrenia (SCZ) is a chronic and complex mental disorder with poorly recognized basic characteristics. It is accompanied by numerous genetic and environmental factors, which has a significant impact on the response to treatment. Epigenetic mechanisms, such as DNA methylation, substantially contribute to the dysregulation of SCZ-associated genes. Thus, this study aimed to investigate the role of DNA methylation in the 5-HT1A receptor gene and its potential collaboration with SCZ’s etiology, focusing on how epigenetic alterations may influence serotonergic neurotransmission and lead to neurodevelopmental features of this disorder. Methods: In the present study, the DNA methylation level of the HTR1A gene promoter (the 5-HT1A receptor) in the peripheral blood mononuclear cells (PBMCs) of 100 patients with SCZ and 100 healthy control subjects was assessed using the high-resolution melting (HRM) method. Genomic DNA was extracted from PBMCs, and following bisulfite conversion, the HRM method was used to quantify the methylation rates in the 5′ promoter region of the HTR1A gene. Results: Based on the results, a significant increase was detected in mean methylation in individuals with SCZ (P<0.001). Moreover, the analysis of receiver operating characteristic curve demonstrated an area under the curve of 0.678, indicating the epigenetic dysregulation of serotonergic signaling in SCZ. Conclusion: Our findings revealed higher DNA methylation in the HTR1A gene promoter region in SCZ patients’ PBMCs compared to healthy controls. To discover the biological mechanisms and clinical significance of epigenetic alterations, future studies should concentrate on brain tissue and gene expression.