Epigenetic alterations of the oxytocin receptor gene in obsessive-compulsive disorder

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.

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T102C and –1438 G/A polymorphisms of the 5-HT2A receptor gene in Turkish patients with obsessive–compulsive disorder

European Psychiatry ◽

10.1016/s0924-9338(03)00066-x ◽

2003 ◽

Vol 18 (5) ◽

pp. 249-254 ◽

Cited By ~ 32

Author(s):

Şenel Tot ◽

M. Emin Erdal ◽

Kemal Yazıcı ◽

Aylin Ertekin Yazıcı ◽

Özmen Metin

Keyword(s):

Obsessive Compulsive Disorder ◽

Receptor Gene ◽

Clinical Severity ◽

Genotype Distribution ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Increased Risk ◽

T102c Polymorphism ◽

Turkish Patients

AbstractObjectiveThis study aimed to investigate the possible association between T102C and –1438 G/A polymorphism in the 5-HT2A receptor gene and susceptibility to and clinical features of obsessive–compulsive disorder (OCD).MethodFifty-eight patients with OCD and 83 healthy controls were included in the study. All patients were interviewed and rated by Yale-Brown Obsessive–Compulsive Scale. T102C and –1438 G/A polymorphisms of 5-HT2A receptor gene were determined by PCR technique in DNAs of peripheral leucocytes.ResultsOCD patients and healthy controls did not show significant differences in genotype distribution for both polymorphisms investigated. We found that frequencies of the TT genotype for T102C polymorphism and the AA genotype for –1438 G/A polymorphism were significantly higher in patients with severe OCD compared to those with moderate or moderate–severe OCD.ConclusionThe –1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with an increased risk of OCD. Our data suggest that the TT genotype of T102C and the AA genotype of –1438 G/A polymorphism might be a factor in clinical severity of OCD.

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