Chun Il Park1,2, Hae Won Kim2,3, Sumoa Jeon2, Jee In Kang4,5, Se Joo Kim6,7. 1. Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. 2. Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Department of Medical Education, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Department of Psychiatry, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, 03722, Republic of Korea. jeeinkang@yuhs.ac. 5. Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. jeeinkang@yuhs.ac. 6. Department of Psychiatry, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, 03722, Republic of Korea. kimsejoo@yuhs.ac. 7. Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. kimsejoo@yuhs.ac.
Abstract
BACKGROUND: Oxytocin is an important neuromodulator involved in cognition and socio-emotional processing that exerts its central activities via oxytocin receptors. Epigenetic alterations in the oxytocin receptor gene (OXTR) may be a molecular mechanism in the pathogenesis of obsessive-compulsive disorder (OCD). This study investigated the association between OXTR DNA methylation and the OCD status of a Korean population. RESULTS: Quantitative leukocyte DNA methylation levels of three cytosine-phosphate-guanine (CpG) sites in the 5' untranslated region (UTR) of OXTR exon 2 and eight CpG sites within OXTR exon 3 were analyzed using the pyrosequencing method in 151 patients with OCD (including 45 drug-naïve patients) and 108 healthy controls. DNA methylation levels were compared between the groups using multiple analyses of covariance separately by sex after controlling for age and educational level. Patients with OCD showed significantly lower methylation levels at CpG1 and CpG2 sites on the UTR of OXTR exon 2 than those of healthy controls for both sexes. In a subset of 45 drug-naïve patients with OCD, the DNA methylation levels also remained significantly lower than those in the controls and their CpG1 methylation levels were significantly negatively associated with the ordering symptom dimension. CONCLUSIONS: Our findings suggest that epigenetic OXTR alterations may affect the pathophysiology of OCD. The potential role of the oxytocin system in OCD development and treatment warrants further investigation.
BACKGROUND:Oxytocin is an important neuromodulator involved in cognition and socio-emotional processing that exerts its central activities via oxytocin receptors. Epigenetic alterations in the oxytocin receptor gene (OXTR) may be a molecular mechanism in the pathogenesis of obsessive-compulsive disorder (OCD). This study investigated the association between OXTR DNA methylation and the OCD status of a Korean population. RESULTS: Quantitative leukocyte DNA methylation levels of three cytosine-phosphate-guanine (CpG) sites in the 5' untranslated region (UTR) of OXTR exon 2 and eight CpG sites within OXTR exon 3 were analyzed using the pyrosequencing method in 151 patients with OCD (including 45 drug-naïve patients) and 108 healthy controls. DNA methylation levels were compared between the groups using multiple analyses of covariance separately by sex after controlling for age and educational level. Patients with OCD showed significantly lower methylation levels at CpG1 and CpG2 sites on the UTR of OXTR exon 2 than those of healthy controls for both sexes. In a subset of 45 drug-naïve patients with OCD, the DNA methylation levels also remained significantly lower than those in the controls and their CpG1 methylation levels were significantly negatively associated with the ordering symptom dimension. CONCLUSIONS: Our findings suggest that epigenetic OXTR alterations may affect the pathophysiology of OCD. The potential role of the oxytocin system in OCD development and treatment warrants further investigation.
Entities:
Keywords:
DNA methylation; Epigenetics; OXTR; Obsessive-compulsive disorder; Oxytocin
Authors: Miriam A Schiele; Jan Lipovsek; Pascal Schlosser; Michael Soutschek; Gerhard Schratt; Michael Zaudig; Götz Berberich; Anna Köttgen; Katharina Domschke Journal: Transl Psychiatry Date: 2022-06-01 Impact factor: 7.989
Authors: Joshua S Danoff; Kelly L Wroblewski; Andrew J Graves; Graham C Quinn; Allison M Perkeybile; William M Kenkel; Travis S Lillard; Hardik I Parikh; Hudson F Golino; Simon G Gregory; C Sue Carter; Karen L Bales; Jessica J Connelly Journal: Clin Epigenetics Date: 2021-01-30 Impact factor: 6.551