Plasma Oxytocin Levels in Untreated Adult Obsessive-Compulsive Disorder Patients

Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Catena-Dell’Osso, Mario; Piccinni, Armando; Massimetti, Gabriele; Dell’Osso, Liliana

doi:10.1159/000438756

Cited by 34 publications

(22 citation statements)

References 75 publications

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“…Indeed, a properly regulated OT system has been suggested to enhance resilience and to act as a hurdle against the development of mental disorders and/or substance abuse [49, 50]. Accumulating evidence suggests a role for OT in the pathophysiology of different psychopathological conditions, mainly in those characterized by social and emotional deficits [3, 29, 30, 51, 52], such as depression [53-56], social phobia [57], anxiety disorders [3], autism spectrum disorders [58, 59], OCD [60, 61], post traumatic stress disorders [9], and other conditions [61-63] almost all characterized by a female preponderance [64, 65]. Again, sex-related OT differences have been related to emotional distress [28, 66] and to the anxiety of a love relationship [36, 67].…”

Section: Discussionmentioning

confidence: 99%

Sex-Related Differences in Plasma Oxytocin Levels in Humans

Marazziti¹,

Baroni²,

Mucci³

et al. 2019

CPEMH

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Background: Increasing evidence supports a key role of Oxytocin (OT) as a modulator of social relationships in mammals. Objective: The aim of the present study was to investigate possible sex-related differences in plasma OT levels in human beings. Methods: Forty-five healthy men and 45 women (mean age: 34.9 ± 6.2 years), were included in the study. Plasma preparation, peptide extraction and OT radioimmunoassay were carried out according to standardized methods. Results: The results showed that OT plasma levels (pg ̸ ml, mean ± SD) were significantly higher in women than in men (4.53 ± 1.18 vs 1.53 ± 1.19, p ˂ 0.001). Conclusions: The present finding demonstrates sex-related differences in plasma OT levels in humans. It is tempting to hypothesize that such differences might be related to behaviours, attitudes, as well as susceptibility to stress response, resilience and social emotions specific of women and men.

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Section: Discussionmentioning

confidence: 99%

Sex-Related Differences in Plasma Oxytocin Levels in Humans

Marazziti¹,

Baroni²,

Mucci³

et al. 2019

CPEMH

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“…In rats, oxytocin injection into the central nucleus of the amygdala has been shown to induce hypergrooming, assumed to reflect OCD-related behavior [14]. Accordingly, elevated plasma and cerebrospinal fluid oxytocin levels were found in OCD [15,16]. On an epigenetic level, increased OXTR exon III methylation was discerned in OCD patients compared to healthy controls [12].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

Schiele¹,

Thiel²,

Kollert³

et al. 2020

Psychother Psychosom

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Introduction: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. Objective: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. Methods: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. Results: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. Conclusions: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.

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“…Alterations in the oxytocin signalling pathway could explain findings by Chatzittofis et al, who observed HPA axis dysregulation in men with hypersexual disorder [3]. Furthermore, studies indicate that oxytocin may be involved in the pathophysiology of obsessive-compulsive disorder [63]. The interaction of oxytocin with the dopamine system, the HPA-axis and the immune system led to the postulation that individual differences in oxytocin levels are impacting addiction vulnerability [64].…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes

et al. 2019

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Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification 'Compulsive Sexual Behavior Disorder' is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD-cg18222192 (MIR708)(p < 10E-05, p FDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, p FDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.

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Plasma Oxytocin Levels in Untreated Adult Obsessive-Compulsive Disorder Patients

Cited by 34 publications

References 75 publications

Sex-Related Differences in Plasma Oxytocin Levels in Humans

Sex-Related Differences in Plasma Oxytocin Levels in Humans

Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes

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