The Role of Endogenous Oxytocin in Anxiolysis: Structural and Functional Correlates

Lancaster, Katie; Goldbeck, Lauren; Pournajafi-Nazarloo, Hossein; Connelly, Jessica J.; Carter, C. Sue; Morris, J. P.

doi:10.1016/j.bpsc.2017.10.003

Cited by 24 publications

(17 citation statements)

References 70 publications

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“…Notably, our finding that OXTR methylation predicts amygdala gray matter volume is consistent with our previous research demonstrating that low plasma oxytocin was associated with increased gray matter in the right central amygdala (Lancaster et al , 2018 ). Here, we have replicated this structural association using OXTR methylation: participants with high OXTR methylation—which is thought to reflect a dampening or reduced efficiency of the endogenous oxytocin system (Kusui et al , 2001 )—is associated with increased gray matter in the right central amygdala.…”

Section: Discussionsupporting

confidence: 92%

“…Our results demonstrate that OXTR methylation is negatively associated with resting parasympathetic tone and that this relationship is mediated by structural differences in the central amygdala. High levels of OXTR methylation have previously been associated with an increase of amygdala reactivity to aversive stimuli (Puglia et al , 2015 ), a pattern of neural reactivity that is supported by studies investigating the effects of exogenous (Kirsch et al , 2005 ) and endogenous oxytocin (Lancaster et al , 2018 ). Because oxytocin signaling has been implicated in anxiolysis, a downtuning of the oxytocin system via DNA methylation of OXTR is assumed to have anxiogenic consequences, but its specific relationship with the autonomic nervous system had not yet been characterized.…”

Section: Discussionmentioning

confidence: 80%

“…In humans, intranasal oxytocin administration modulates amygdala blood oxygen level dependent (BOLD) response, most often observed as a reduction in amygdala reactivity to aversive stimuli (Kirsch et al , 2005 ; Domes et al , 2007 ; Labuschagne et al , 2010 ). Similarly, this attenuation of amygdala reactivity has also been observed as a function of participants own endogenous (plasma) oxytocin levels (Lancaster et al , 2018 ). Finally, oxytocin’s amygdalar connection is also reflected in structural differences in the human amygdala: participants with lower endogenous oxytocin levels and carriers of an oxytocin receptor gene (OXTR) single nucleotide polymorphism risk-allele showed increased gray matter density within the amygdala (Tost et al , 2010 ; Andari et al , 2014 ; Lancaster et al , 2018 ), pointing toward an enduring relationship between the oxytocinergic system and the subcortical brain structure.…”

Section: Introductionmentioning

confidence: 71%

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DNA methylation ofOXTRis associated with parasympathetic nervous system activity and amygdala morphology

Lancaster

Goldbeck

Puglia

et al. 2018

Social Cognitive and Affective Neuroscience

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Oxytocin has anxiolytic properties whose mechanisms of action are still being identified. DNA methylation in the promoter region of the oxytocin receptor gene (OXTR), an epigenetic modification that putatively reflects a downtuning of the oxytocin system, has previously been implicated in the regulation of fear-related responses through the amygdala. In this study, we attempted to characterize the relationship between methylation of OXTR and anxiogenesis using two distinct endophenotypes: autonomic nervous system activity and subcortical brain structure. In 79 participants, we found that increased OXTR methylation is associated with attenuated resting parasympathetic tone, measured using high-frequency heart rate variability. Further, we found that this relationship is mediated by brain morphology, such that OXTR methylation is associated with increased gray matter of the central amygdala which is, in turn, associated with decreased parasympathetic tone. These results further our understanding of epigenetic regulation of the human oxytocin system and its role in anxiogenesis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 71%

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DNA methylation ofOXTRis associated with parasympathetic nervous system activity and amygdala morphology

Lancaster

Goldbeck

Puglia

et al. 2018

Social Cognitive and Affective Neuroscience

Self Cite

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“…It is unknown whether salivary oxytocin increase corresponds to the change in the brain activity in a linear way, but it can be expected that the neural effects of conditioned oxytocin release might be much smaller than the effects of oxytocin administration. However, even small natural variations of the endogenous oxytocin levels have been shown to affect brain activity, for example, in resting state [51], during massage [52], and in response to aversive stimuli [53]. Therefore, it could be expected that endogenous oxytocin release triggered by conditioning, would be strong enough to affect brain activity.…”

Section: Plos Onementioning

confidence: 99%

Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study

et al. 2020

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It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well. PLOS ONEPLOS ONE | https://doi.org/10.

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“…Recent evidence shows that salivary oxytocin in dogs is significantly increased after affiliative human–dog interaction ( MacLean et al, 2017 ). This is relevant since oxytocin may promote socialization by its anxiolytic effects ( Lancaster et al, 2017 ); for instance by promoting social play, especially in novel situations (for a review Kis et al, 2017 ). Similarly, recent evidence shows the effects of intranasal OT administration on dog behavior ( Romero et al, 2014 ; Kis et al, 2015 ; Nagasawa et al, 2015 ; Oliva et al, 2015 ; Romero et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Hormonal Correlates of Exploratory and Play-Soliciting Behavior in Domestic Dogs

et al. 2018

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Exploration and play are considered to be crucial behaviors during mammalian development. Even though the relationship between glucocorticoids and exploratory behavior, stress, and anxiety is well described in the literature, very little is known about their role in play behavior in non-rodents. Likewise, the functional role of the “social hormone” oxytocin in exploration, play, stress, and anxiety is still unknown. The present work addresses this literature gap by studying plasma hormone profiles for cortisol (CORT) and oxytocin (OT) of domestic dogs exposed to a novel arena containing two unfamiliar trainers who did not interact with the dogs. We provide evidence suggesting a functional relationship between hormonal measures of cortisol and oxytocin and adaptive behavior (play-soliciting and exploration) in freely behaving domestic dogs. We have taken into account several possible factors in our analyses and interpretations, from the nature and quality of the measurements to demographic factors to statistical robustness. Our results indicate that reduced CORT levels are associated with increments of both play-soliciting behavior frequency and exploratory behavior duration. Furthermore, taken together, our data and our simulations suggest a relationship between OT and the enactment of play-soliciting behaviors by freely behaving domestic dogs that must be further investigated. Future studies should consider naturalistic structured and semi-structured experimental approaches linking behavior with (neuro) physiological measures, taking into account demographic factors such as age and relevant interphase factors such as the sex of the dog; and socio-historic factors such as the playfulness of the dog, history of interaction with young humans, among others, to take full account of interaction between humans and animals in comparative studies (Parada and Rossi, 2018).

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The Role of Endogenous Oxytocin in Anxiolysis: Structural and Functional Correlates

Cited by 24 publications

References 70 publications

DNA methylation ofOXTRis associated with parasympathetic nervous system activity and amygdala morphology

DNA methylation ofOXTRis associated with parasympathetic nervous system activity and amygdala morphology

Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study

Hormonal Correlates of Exploratory and Play-Soliciting Behavior in Domestic Dogs

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