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

Abstract

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.

Is Oxytocin “Nature’s Medicine”?

“…The variable expression in tissues of OXTR is also epigenetically tuned by early life experience (Baker et al, 2017;Krol et al, 2019a;Perkeybile et al, 2019), increasing the capacity of peptides to have complex adaptive functions. Evidence in humans for the functional importance of the oxytocin genetic-epigenetic systems at present comes primarily from correlations among genetic and epigenetic variations in the OXTR gene and individual differences in behavior, physiology, and brain anatomy (Rodrigues et al, 2009;Tost et al, 2010;Jack et al, 2012;Puglia et al, 2015;Lancaster et al, 2018b).…”

Heart rate variability: Evaluating a potential biomarker of anxiety disorders

“…Additional hypothesis‐driven genetic studies of HRV are summarized in Table 3 (Busjahn et al., 1998; Chang et al., 2015, 2019; Chang, Fang, et al., 2014; Kanthak et al., 2016; Klusek et al., 2017; Lancaster et al., 2018; Neumann et al., 2005; Nishikino et al., 2006; Riese et al., 2014). Some of these studies have included the exploration of anxiety‐related phenotypes.…”

A novel role of oxytocin: Oxytocin-induced well-being in humans

“…For example, the receptors were located in the olfactory nucleus, the hypothalamus, the amygdala, the septum, the paraventricular nucleus, and so forth. In particular, oxytocin receptors have been recently confirmed in the autonomic nervous system [64]. More recently, a study using oxytocin receptor-Venus mice provided a detailed distribution of oxytocin receptors at the cellular level [65].…”