Oxytocin and Vasopressin Are Dysregulated in Williams Syndrome, a Genetic Disorder Affecting Social Behavior

Abstract

The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS), a condition caused by deletion of ∼28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT) and arginine vasopressin (AVP) regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music), and a negative physical stressor (cold). We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior.

Linking social behaviour and anxiety to attention to emotional faces in Williams syndrome

“…Furthermore, on the basis of the regulatory effect of the neuropeptide oxytocin on social behaviour, amygdalar responses and eye gaze (Gamer et al, 2009;Gamer et al, 2010), it will be important for future studies to explore the relationship between endogenous levels of oxytocin, amygdala reactivity and individual differences in anxiety and gaze behaviour toward emotional faces in WS. Together these future studies would provide a more detailed understanding of the role of the amygdala in attention allocation to emotional facial expressions and clarify the previously reported variations in social behaviour in WS (Dai et al, 2012;Haas et al, 2010).…”

Integrative Approaches Utilizing Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to Autistic Social Dysfunction

“…Animal models: oxytocin, functional neural connectivity, and the promotion of social cohesion during an environmental stressor Although there is mounting evidence implicating OT in socioemotional disorders in humans (Jacob et al, 2007;Rubin et al, 2011;Dai et al, 2012), research using animal models, including rats, sheep, and mice (Winslow et al, 2000;Choleris et al, 2007;Leng et al, 2008;Nowak et al, 2011;Gabor et al, 2012), has been a catalyst by identifying basic behavioral processes, such as social recognition, parental bonding, and social antagonism, mediated or modulated by OT that become dysregulated in human mental illness. Prairie voles, in particular, have been useful in revealing OT's role in human sociality largely because they share with humans the tendency toward forming selective preferences for familiar conspecifics (Williams et al, 1992).…”

Intranasal oxytocin increases covert attention to positive social cues

“…These differences in social phenotype seem to be reflected in gaze behavior : autistic individuals display reduced attentional capture by facial stimuli and avoidance of eye gaze (Riby & Hancock, 2009 ;Kliemann et al 2010) whereas individuals with Williams syndrome show enhanced gazing towards facial picture components, the eye regions of faces and happy facial expressions (Riby & Hancock, 2009 ;Dodd & Porter, 2010 ;Porter et al 2010 ;Moore et al 2012). Notably, both syndromes have recently been linked to alterations in the OT system (Campbell et al 2011 ;Dai et al 2012 ;Pobbe et al 2012).…”