Methylation of the <i>OXTR</i> gene in women with anorexia nervosa: Relationship to social behavior

Thaler, Lea; Brassard, Sarah L.; Booij, Linda; Kahan, Esther; McGregor, Kevin; Labbe, Aurélie; Israël, Mimi; Steiger, Howard

doi:10.1002/erv.2703

Cited by 19 publications

(14 citation statements)

References 33 publications

(31 reference statements)

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“…For example, evidence has emerged demonstrating a role of oxytocin in the AN disease process. The operative mechanism may be related to homeostatic and reward-related processes involved in the regulation of food intake, but also via pathways involving attachment experiences and social cognition, all of which are impaired in AN (Giel, Zipfel, & Hallschmid, 2018;Thaler et al, 2020).…”

Section: Pharmacologic Interventionsmentioning

confidence: 99%

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality

Wonderlich

Bulik

Schmidt

et al. 2020

Intl J Eating Disorders

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100

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Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE-AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE-AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE-AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE-AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE-AN and their families. K E Y W O R D S anorexia nervosa, disordered eating, eating disorders, severe and enduring anorexia nervosa Anorexia nervosa (AN) is most common in girls and young women with a lifetime prevalence in women of up to 2-4% (Galmiche, Dechelotte,

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Section: Pharmacologic Interventionsmentioning

confidence: 99%

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality

Wonderlich

Bulik

Schmidt

et al. 2020

Intl J Eating Disorders

Self Cite

100

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“…Therefore, females appear to be more prone to epigenetic changes in OXTR following stress events than males, which may reflect the sex-dependent effect of oxytocin on stress responsivity. Moreover, hypermethylation of CpG sites at OXTR gene has been reported in patients with anorexia-nervosa [ 77 ], as well as in patients with autism spectrum disorders (ASD) [ 78 ] compared with healthy control subjects. On the other hand, reduced levels of OXTR methylation in the cord blood of newborns has been associated with maternal depression symptoms in the second trimester of pregnancy [ 79 ].…”

Section: Epigenetic Alterations As a Cause Of Dysregulation Of The Stress Responsementioning

confidence: 99%

Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders

Mourtzi

Sertedaki

Charmandari

2021

IJMS

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Stress is defined as a state of threatened or perceived as threatened homeostasis. The well-tuned coordination of the stress response system is necessary for an organism to respond to external or internal stressors and re-establish homeostasis. Glucocorticoid hormones are the main effectors of stress response and aberrant glucocorticoid signaling has been associated with an increased risk for psychiatric and mood disorders, including schizophrenia, post-traumatic stress disorder and depression. Emerging evidence suggests that life-stress experiences can alter the epigenetic landscape and impact the function of genes involved in the regulation of stress response. More importantly, epigenetic changes induced by stressors persist over time, leading to increased susceptibility for a number of stress-related disorders. In this review, we discuss the role of glucocorticoids in the regulation of stress response, the mechanism through which stressful experiences can become biologically embedded through epigenetic alterations, and we underline potential associations between epigenetic changes and the development of stress-related disorders.

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“…These studies have generally focused on two regions of the OXTR gene: MT2 (covering much of exon 1 and some of intron 1) and exon 3. For example, dysregulated DNA methylation in MT2 has been associated with autism [14], callous-unemotional traits [17,18], anorexia nervosa [19,20], schizoaffective disorders [21,22], post-partum depression [23], attachment anxiety [24], obsessive compulsive disorder [25], and anxiety and depression [26]. DNA methylation in MT2 is associated with neural endophenotypes in typical populations: DNA methylation is positively correlated with brain activity during animacy perception [27], emotion perception [28,29], and social attention [30].…”

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confidence: 99%

Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression

et al. 2021

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Background The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. Results Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3′ portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. Conclusions These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3′ portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3′ portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.

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Methylation of the OXTR gene in women with anorexia nervosa: Relationship to social behavior

Cited by 19 publications

References 33 publications

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality

Severe and enduring anorexia nervosa: Update and observations about the current clinical reality

Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders

Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression

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