Greg J. Norman

Oxytocin increases autonomic cardiac control: Moderation by loneliness

The current study examined the role of perceived social isolation in moderating the effects of oxytocin on cardiac autonomic control in humans. Intranasal administration of 20 IU oxytocin resulted in a significant increase in autonomic (parasympathetic and sympathetic) cardiac control. Specifically, oxytocin increased high frequency heart rate variability, a relatively pure measure of parasympathetic cardiac control, and decreased pre-ejection period, a well-validated marker of enhanced sympathetic cardiac control. Derived metrics of autonomic co-activity and reciprocity revealed that oxytocin significantly increased overall autonomic cardiac control. Furthermore, the effects of oxytocin on cardiac autonomic control were significantly associated with loneliness ratings. Higher levels of loneliness were associated with diminished parasympathetic cardiac reactivity to intranasal oxytocin. The effects of OT on autonomic cardiac control were independent of any effects on circulating pro-inflammatory cytokine or stress hormone levels. Thus, lonely individuals may be less responsive to the salubrious effects of oxytocin on cardiovascular responsivity.

A neurobehavioral evolutionary perspective on the mechanisms underlying empathy

In mammals, empathy is crucial for living in social groups and caring for others. In this paper, we consider the structural and functional organization of empathy. We propose that empathy subsumes a variety of neurobiological processes and partially dissociable information processing subsystems, each of which has a unique evolutionary history. Even the most advanced and flexible forms of empathy in humans are built on more basic forms and remain connected to core subcortical and neurohormonal mechanisms associated with affective communication, parental care and social attachment processes. Considering empathy within a framework that recognizes both the continuities and the changes within a phylogenetic perspective provides a richer understanding of empathy and related neurobehavioral processes.

Social isolation alters neuroinflammatory response to stroke

Social isolation has dramatic long-term physiological and psychological consequences; however, the mechanisms by which social isolation influences disease outcome are largely unknown. The purpose of the present study was to investigate the effects of social isolation on neuronal damage, neuroinflammation, and functional outcome after focal cerebral ischemia. Male mice were socially isolated (housed individually) or pair housed with an ovariectomized female before induction of stroke, via transient intraluminal middle cerebral artery occlusion (MCAO), or SHAM surgery. In these experiments, peri-ischemic social isolation decreases poststroke survival rate and exacerbates infarct size and edema development. The social influence on ischemic damage is accompanied by an altered neuroinflammatory response; specifically, central interleukin-6 (IL-6) signaling is down-regulated, whereas peripheral IL-6 is up-regulated, in isolated relative to socially housed mice. In addition, intracerebroventricular injection of an IL-6 neutralizing antibody (10 ng) eliminates social housing differences in measures of ischemic outcome. Taken together, these data suggest that central IL-6 is an important mediator of social influences on stroke outcome.

Effects of social isolation on glucocorticoid regulation in social mammals.

The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans.

Selective influences of oxytocin on the evaluative processing of social stimuli

The neuropeptide oxytocin has been implicated in a wide range of social processes, such as pair bonding, affiliation, and social judgments that may contribute to normal adjustment and psychiatric states. The present experimental study sought to elucidate potential underlying mechanisms by which oxytocin may impact social processes by examining the effects of intranasal oxytocin on basic evaluative processes. Subjects rated slide stimuli from the International Affective Picture System, varying across multiple categories (pleasant, neutral, unpleasant) and social content. Separate ratings for arousal and for the positive and negative components of valence were obtained in the context of a bivariate evaluative space model. Oxytocin did not have an independent significant effect on positivity or negativity ratings, but instead oxytocin treatment altered the interaction between these component processes for social, relative to non-social stimuli regardless of valence conditions. Specifically, oxytocin, relative to vehicle, significantly decreased arousal ratings to threatening human stimuli without altering ratings of threatening animal stimuli. These results indicate that oxytocin may exert its effects through dynamic alterations in the partially separable neural substrates mediating arousal as well as positive and negative evaluations of social stimuli.

The Insula and Evaluative Processes

The insula has been implicated as a component of central networks subserving evaluative and affective processes. This study examined evaluative valence and arousal ratings in response to picture stimuli in patients with lesions of the insula and two contrast groups: a control-lesion group (the primary contrast group) and an amygdala-lesion group. Patients rated the positivity and negativity of picture stimuli (from very unpleasant to very pleasant) and how emotionally arousing they found the pictures to be. Compared with patients in the control-lesion group, patients with insular lesions reported reduced arousal in response to both unpleasant and pleasant stimuli, as well as marked attenuation of valence ratings. In contrast, the arousal ratings of patients with amygdala lesions were selectively attenuated for unpleasant stimuli, and these patients’ positive and negative valence ratings did not differ from those of the control-lesion group. Results support the view that the insular cortex may play a broad role in integrating affective and cognitive processes, whereas the amygdala may have a more selective role in affective arousal, especially for negative stimuli.

Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others

Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, 51 male participants (18–35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the affective experiences of other conspecifics.

Social Interaction Prevents the Development of Depressive-Like Behavior Post Nerve Injury in Mice: A Potential Role for Oxytocin

Objective: To examine the salubrious role of social interaction in modulating the development of allodynia (increased sensitivity to typically innocuous physical stimuli) and depressive-like behavior post peripheral nerve injury in mice. The determination of potential mechanisms that mediate social influences on the behavioral and physiological response to peripheral nerve injury. Methods: Mice were pair housed or socially isolated for 2 weeks before spared nerve injury (SNI). Animals were cannulated; socially isolated animals were centrally treated with oxytocin; and socially paired animals were centrally treated with an oxytocin receptor antagonist. Animals were subsequently monitored for the development of mechanical allodynia and depressive-like behavior, and tissue was collected for analysis of the central levels of the cytokine interleukin 1 beta (IL-1&bgr;). Results: Depressive-like behavior was assessed via the Porsolt forced swim test, developed only among socially isolated mice with nerve injury. Socially isolated mice with nerve injury also were the only experimental group to exhibit increased frontal cortex IL-1&bgr; gene expression on day 7 post injury. Moreover, central treatment of socially isolated mice with oxytocin, a neuropeptide associated with social bonding, attenuated the effects of SNI on depressive-like behavior and reduced frontal cortex IL-1&bgr; protein levels in socially isolated animals. Conversely, pair-housed animals treated with a selective oxytocin receptor antagonist developed depressive-like behavior equivalent to that of socially isolated animals and displayed increased IL-1&bgr; protein levels within the frontal cortex. Conclusion: These data suggest that social interaction significantly alters the affective and neuroinflammatory responses to SNI through a mechanism that could involve oxytocin. ELISA = enzyme-linked immunosorbent assay; FST = forced swim task; ICV = intracerebroventricular; IL-1&bgr; = interleukin-1&bgr;; ISO = isolated; OTA = oxytocin receptor antagonist; PAG = periaqueductal gray; PFC = prefrontal cortex; POD = postoperative day; SNI = spared nerve injury; VEH = vehicle.

Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function: A population based study

Oxytocin (OT) is a nonapeptide neurohormone that is involved in a broad array of physiological and behavioral processes related to health including hypothalamic-pituitary-adrenal (HPA) axis functioning, autonomic nervous system (ANS) activity and social behaviors. The present study sought to explore the influence of genetic variation in the oxytocin receptor (SNP; rs53576) on autonomic and neurohormonal functioning across both resting and psychological stress conditions in a population based sample of older adults. Results revealed that A carrier males showed higher levels of resting sympathetic cardiac control as compared to their G/G counter parts. However, G/G participants displayed significantly higher levels of sympathetic reactivity to psychological stress with G/G males showing the highest levels of sympathetic response to stress. Although no significant effects were detected for heart rate or parasympathetic cardiac control across resting and stress conditions, results revealed that G/G participants generally displayed heightened stroke volume and cardiac output reactivity to the psychological stressor. Furthermore, analysis of diurnal fluctuations in salivary cortisol revealed that G/G participants displayed lower awakening cortisol levels and less variation in salivary cortisol across the day as compared to A carrier individuals.

Social neuroscience: The social brain, oxytocin, and health

Complex social behaviors allow various social organisms to create emergent organizations that extend beyond the individual. Social neuroscience is a burgeoning field that strives to understand the genetic, hormonal, and neural mechanisms responsible for these social structures and behaviors. Consequently, social neuroscience is highly interdisciplinary in nature and embraces the application of methods ranging from the molecular to the molar to investigate the reciprocal interactions between biological, cognitive, and social levels of analysis. The broad scope of such an endeavor introduces particular challenges associated with the integration of multiple levels of analysis. In the present mini-review, we highlight some recent findings in the field of social neuroscience and demonstrate the potential benefits of applying multilevel integrative analysis to the study of social behavior and its influence on physiology and health.