Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive–compulsive disorder

Abstract

Background Obsessive–compulsive disorder (OCD) is a chronic neurodevelopmental disorder that affects up to 3% of the general population. Although epigenetic mechanisms play a role in neurodevelopment disorders, epigenetic pathways associated with OCD have rarely been investigated. Oxytocin is a neuropeptide involved in neurobehavioral functions. Oxytocin has been shown to be associated with the regulation of complex socio-cognitive processes such as attachment, social exploration, and social recognition, as well as anxiety and other stress-related behaviors. Oxytocin has also been linked to the pathophysiology of OCD, albeit inconsistently. The aim of this study was to investigate methylation in two targets sequences located in the exon III of the oxytocin receptor gene (OXTR), in OCD patients and healthy controls. We used bisulfite sequencing to quantify DNA methylation in peripheral blood samples collected from 42 OCD patients and 31 healthy controls. ResultsWe found that the level of methylation of the cytosine-phosphate-guanine sites in two targets sequences analyzed was greater in the OCD patients than in the controls. The higher methylation in the OCD patients correlated with OCD severity. We measured DNA methylation in the peripheral blood, which prevented us from drawing any conclusions about processes in the central nervous system.ConclusionTo our knowledge, this is the first study investigating DNA methylation of the OXTR in OCD. Further studies are needed to evaluate the roles that DNA methylation and oxytocin play in OCD.

Increased methylation of the oxytocin receptor gene in motor functional neurological disorder: a preliminary study

“…Although preliminary, these findings are of particular interest for potential novel future treatment approaches, such as intranasal oxytocin administration in FND. It has to be stressed out, though, that OXTR methylation has also been found to be elevated in other neuropsychiatric disorders, such as obsessive compulsive disorder7 and anorexia8 questioning the specificity of our findings to FND. Further research is needed and larger cohorts of patients taking in account all multiple factors that contribute to FND.…”

The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review

“…Two studies examining OXTR DNAm in the exon 3 region from blood and anxiety disorders were identified [ 53 , 54 ]. Ziegler et al, investigated 110 adults with social anxiety compared to 110 healthy controls and noted reduced DNAm at only one of twelve CpG OXTR exon 3 sites on psychological, cortisol response and fMRI measures [ 54 ]. When average DNAm was considered across all twelve CpG sites, reduced methylation was also observed compared to controls.…”

Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders

“…OXTR has been the focus of extensive genetic and epigenetic studies for its role in psychiatric diseases or morbid behaviors in humans. There are more than 20 studies focusing on analysis of 5mC in the different CpG sites within the CpG island in humans (Supplemental Figure 10) (14,17,(54)(55)(56)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92). The regions equivalent to the hypermethylated BS1 and BS2 in Tet1 mutant mice have been the focus in these studies.…”