Increased Temporal Discounting in Social Anxiety Disorder Normalizes after Oxytocin Treatment

Hurlemann, René; Scheele, Dirk; Kinfe, Thomas M.; Berger, Ruben; Philipsen, Alexandra; Voncken, Marisol J.; Kuypers, Kim P. C.; Schruers, Koen

doi:10.1159/000495259

Cited by 14 publications

(8 citation statements)

References 10 publications

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“…Accordingly, the presently observed increased OXTR exon III methylationand thus presumably heightened oxytocinergic transmission -conferring impaired treatment response is furthermore in accordance with elevated plasma as well as cerebrospinal fluid oxytocin levels in OCD patients [15,16] and with oxytocin inducing OCD-like behavior in the rodent model [14]. Along these lines, oxytocin administration -although proposed as a treatment adjunct in other mental disorders [23][24][25][26] -has been shown to be ineffective in treating OCD [27,28]. A detrimental role of increased oxytocin in OCD pathogenesis and treatment response could be interpreted in the context of oxytocin having been linked to volitional and emotional ambivalence [29], and an observed strong ambivalence regarding apparently opposing interpersonal styles of prosocial attitudes and latent aggression in OCD [30].…”

Section: Discussionmentioning

confidence: 56%

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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Section: Discussionmentioning

confidence: 56%

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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“…For example, it was recently shown how a higher OXTR methylation level is linked to enhanced infants’ brain responses (as measured via fNIRS) to angry and fearful faces [ 55 ], while other evidence suggests that higher OXTR methylation is associated with problems with facial and emotional recognition [ 56 ]. While there is some evidence that the role of oxytocin administration in social discounting may be modulated by empathy traits [ 57 ], to the best of our knowledge there is only one paper directly investigating the role of oxytocin administration in reducing temporal discounting in a sample affected by social anxiety disorder [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

OXTR Gene DNA Methylation Levels Are Associated with Discounting Behavior with Untrustworthy Proposers

et al. 2022

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Individual differences in temporal and probabilistic discounting are associated with a wide range of life outcomes in literature. Traditional approaches have focused on impulsiveness and cognitive control skills, on goal-oriented personality traits as well as on the psychological perception of time. More recently, literature started to consider the role of social and contextual factors in discounting behavior. Between others, higher generalized trust in human beings and specific trust in people who will deliver the future/probabilistic rewards have been related to a stronger willingness to wait and to assume risk. Moreover, the tendency to trust others has been associated with the oxytocin receptor gene regulation that can be modified by life experiences. In this perspective, we hypothesized that differences in the tendency to wait and to take risks for a more desirable reward according to the proposer’s trustworthiness could be related to a different level of DNA methylation at the oxytocin receptor gene. Findings confirmed that participants are less willing to wait and to risk when the proposer is considered highly untrustworthy and revealed how higher oxytocin receptor gene DNA methylation is associated with a stronger effect due to the presence of an untrustworthy proposer. Limits and future directions are outlined.

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“…A recent meta-analysis confirmed the principle efficacy and safety of IN-OT treatment for PTSD; however, as reflected by preclinical evidence (Lieberz et al, 2020), IN-OT exerts differential, sometimes even opposing, effects in male and female patients with PTSD (Peled-Avron et al, 2020). Modulatory effects of IN-OT (24 IU) on amygdala reactivity (Labuschagne et al, 2010), amygdala-mPFC connectivity (Sripada et al, 2013), and decision-making (Hurlemann et al, 2019) have also been reported for social anxiety disorder; however, the influence of sex as well as the optimal therapeutic dose range for IN-OT in social anxiety disorder are unclear. As a consequence, future clinical trials of IN-OT for anxiety disorders and PTSD should take dose-response as well as person-related effects into account (Andari et al, 2018).…”

Section: Clinical Translation Of the Fear-modulating Effects Of Oxytocinmentioning

confidence: 99%

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

et al. 2021

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Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, increased reactivity to unpredictable versus predictable threat signals, deficits in fear extinction, and an inability to discriminate between threat and safety. First-line pharmacotherapies for psychiatric disorders have limited therapeutic efficacy in PTSD. However, recent studies have advanced our understanding of the roles of several limbic neuropeptides in the regulation of defensive behaviors and in the neural processes that are disrupted in PTSD. For example, preclinical studies have shown that blockers of tachykinin pathways, such as the Tac2 pathway, attenuate fear memory consolidation in mice and thus might have unique potential as early post-trauma interventions to prevent PTSD development. Targeting this pathway might also be beneficial in regulating other symptoms of PTSD, including trauma-induced aggressive behavior. In addition, preclinical and clinical studies have shown the important role of angiotensin receptors in fear extinction and the promise of using angiotensin II receptor blockade to reduce PTSD symptom severity. Additional preclinical studies have demonstrated that the oxytocin receptors foster accurate fear discrimination by facilitating fear responses to predictable versus unpredictable threats. Complementary human imaging studies demonstrate unique neural targets of intranasal oxytocin and compare its efficacy with well-established anxiolytic treatments. Finally, promising data from human subjects have demonstrated that a selective vasopressin 1A receptor antagonist reduces anxiety induced by unpredictable threats. This review highlights these novel promising targets for the treatment of unique core elements of PTSD pathophysiology.

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Increased Temporal Discounting in Social Anxiety Disorder Normalizes after Oxytocin Treatment

Cited by 14 publications

References 10 publications

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

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

OXTR Gene DNA Methylation Levels Are Associated with Discounting Behavior with Untrustworthy Proposers

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

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