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Schizophr Bull. 2019 Apr 9. pii: sbz016. doi: 10.1093/schbul/sbz016. [Epub ahead of print]

Reduced DNA Methylation of the Oxytocin Receptor Gene Is Associated With Anhedonia-Asociality in Women With Recent-Onset Schizophrenia and Ultra-high Risk for Psychosis.

Bang M1, Kang JI2,3, Kim SJ2,3, Park JY3,4, Kim KR2,3, Lee SY3,5, Park K2,3, Lee E2,3, Lee SK6, An SK2,3,7.

Author information

1
Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
2
Department of Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
4
Department of Psychiatry, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
5
Department of Psychiatry, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.
6
Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
7
Graduate Program in Cognitive Science, Yonsei University, Seoul, Republic of Korea.

Abstract

Negative symptoms are recognized as a fundamental feature of schizophrenia throughout the disease course. Epigenetic alterations in the oxytocin receptor gene (OXTR) may be a key mechanism involved in social-emotional disturbances of schizophrenia. Here, we investigated OXTR methylation and its association with clinical and brain network connectivity phenotypes of negative symptoms, particularly anhedonia-asociality, in individuals with recent-onset schizophrenia (ROS) and at ultrahigh risk (UHR) for psychosis. Sixty-four ROS (39 women), 46 UHR (19 women), and 98 healthy individuals (52 women) participated in this study. OXTR methylation was quantified using the pyrosequencing method. A subset of participants (16 ROS, 23 UHR, and 33 healthy controls [HCs]) underwent a 5.5-minute resting-state functional magnetic resonance imaging to determine the relationship between OXTR methylation and the striatal-amygdala network functional connectivity (FC) underlying anhedonia-asociality. Both men and women with ROS and UHR showed significantly decreased OXTR methylation compared to HCs. In women with ROS and UHR, decreased OXTR methylation showed a significant correlation with increased anhedonia-asociality. FC of the striatal-amygdala network, positively associated with the severity of anhedonia-asociality, showed an inverse correlation with OXTR methylation. This study suggests that epigenetic alterations of OXTR, which can be detected before the development of full-blown psychosis, confer susceptibility to schizophrenia and play a crucial role in the manifestation of anhedonia-asociality, particularly in women.

KEYWORDS:

anhedonia-asociality; epigenetics; schizophrenia; ultrahigh risk for psychosis; 
oxytocin receptor gene

PMID:
31220321
DOI:
10.1093/schbul/sbz016

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