Hypermethylation of the oxytocin receptor gene (OXTR) in obsessive-compulsive disorder: further evidence for a biomarker of disease and treatment response

Bey, Katharina; Campos-Martín, Rafael; Klawohn, Julia; Reuter, Benedikt; Grützmann, Rosa; Riesel, Anja; Wagner, Michael; Ramı́rez, Alfredo; Kathmann, Norbert

doi:10.1080/15592294.2021.1943864

Cited by 25 publications

(20 citation statements)

References 66 publications

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“…First, a symptom-based classification differentiating the OCD subtype according to OCI-R and Y-BOCS may include mixed symptoms and affect the study results. Future research could classify precisely based on disease biomarkers using machine learning, such as structural neuroimaging biomarkers [ 66 ], inflammation-related biomarkers [ 67 ], and genetic and epigenetic architecture biomarkers [ 68 , 69 ]. Second, we did not exclude patients with comorbidities or medications.…”

Section: Discussionmentioning

confidence: 99%

Functional Connectivity within the Frontal–Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder

Xie

Song

et al. 2022

Brain Sciences

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Background: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. Results: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. Conclusions: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal–striatal network, which distinguishes OCD from washing OCD.

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Section: Discussionmentioning

confidence: 99%

Functional Connectivity within the Frontal–Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder

Xie

Song

et al. 2022

Brain Sciences

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“…Some results indicated no significant associations between any of several tested SNPs in the OXTR gene [ 103 ], while other studies led to the conclusion that such SNPs can modulate the onset age of this disease, thus, playing an important role in the pathophysiology [ 104 ]. Another discrepancy appeared during studies on DNA methylation in the OXTR locus, as there are reports demonstrating enhanced DNA modification in the cells of patients with obsessive-compulsive disorder [ 105 , 106 ] while other analyses led to the opposite conclusions, pointing to the impaired methylation of OXTR [ 107 ].…”

Section: Oxtr In Mental Disordersmentioning

confidence: 99%

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Pierzynowska

Gaffke

Żabińska

et al. 2023

IJMS

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The oxytocin receptor (OXTR), encoded by the OXTR gene, is responsible for the signal transduction after binding its ligand, oxytocin. Although this signaling is primarily involved in controlling maternal behavior, it was demonstrated that OXTR also plays a role in the development of the nervous system. Therefore, it is not a surprise that both the ligand and the receptor are involved in the modulation of behaviors, especially those related to sexual, social, and stress-induced activities. As in the case of every regulatory system, any disturbances in the structures or functions of oxytocin and OXTR may lead to the development or modulation of various diseases related to the regulated functions, which in this case include either mental problems (autism, depression, schizophrenia, obsessive-compulsive disorders) or those related to the functioning of reproductive organs (endometriosis, uterine adenomyosis, premature birth). Nevertheless, OXTR abnormalities are also connected to other diseases, including cancer, cardiac disorders, osteoporosis, and obesity. Recent reports indicated that the changes in the levels of OXTR and the formation of its aggregates may influence the course of some inherited metabolic diseases, such as mucopolysaccharidoses. In this review, the involvement of OXTR dysfunctions and OXTR polymorphisms in the development of different diseases is summarized and discussed. The analysis of published results led us to suggest that changes in OXTR expression and OXTR abundance and activity are not specific to individual diseases, but rather they influence processes (mostly related to behavioral changes) that might modulate the course of various disorders. Moreover, a possible explanation of the discrepancies in the published results of effects of the OXTR gene polymorphisms and methylation on different diseases is proposed.

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“…The CBT sessions were administered by licensed psychotherapists and conformed to the general conditions for psychotherapy in the public German health care system, typically consisting of 25 or more individual 50-minute sessions per week. Details about the treatment can be found in Bey et al (2021) 54 and Kathmann et al (2022) 55 . For n = 100 patients (n = 54 female, n = 46 male), Y-BOCS data was available at pre-and post-treatment 56 .…”

Section: Treatment Subsamplementioning

confidence: 99%

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response

Ramı́rez

Campos-Martín

Bey

et al. 2023

Preprint

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Obsessive-compulsive disorder (OCD) is a mental disorder affecting 2-3% of the general population. The dynamic nature of epigenetics provides a unique opportunity to find biomarkers of OCD symptoms, clinical progression, and treatment response. Consequently, we analyzed a case-control study on Illumina Methylation EPIC BeadChip from 185 OCD patients and 199 controls. Patients and controls were assessed by trained therapists using the Structured Clinical Interview for DSM-IV. We identified 12 CpGs capable of classifying OCD patients and predicting symptom severity. These CpGs are enriched with the sweet-compulsive brain hypothesis, which proposes that OCD patients may have impaired insulin signaling sensitivity due to abnormal dopaminergic transmission in the striatum. Three of the twelve CpG signals were replicated in an independent study reported in the Han Chinese population. Our findings support the role of epigenetic mechanisms in OCD and may help pave the way for biologically-informed and individualized treatment options.

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Hypermethylation of the oxytocin receptor gene (OXTR) in obsessive-compulsive disorder: further evidence for a biomarker of disease and treatment response

Cited by 25 publications

References 66 publications

Functional Connectivity within the Frontal–Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder

Functional Connectivity within the Frontal–Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response

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