Deregulation of Oxytocin and Vasopressin in Williams Syndrome: A New Model For Exploring Neurogenetics and Neurobiology of Human Social Behavior
Year: 2012
Type: report
Abstract: The molecular and neural mechanisms regulating 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. OverviewGiven the complex cognitive processes that are implied, the scientific investigation of social behavior and attachment is extremely difficult, especially in humans.Using a relatively simple human genetic model (WS) characterized by profound disturbances in social relationships, this very nice study provides new convincing experimental evidence that the neuropeptides OT and, although to a lesser extent, AVP are intimately involved in the control of human social behavior.Since many years now, in intimate association with forebrain reinforcing dopamine pathways, OT and AVP have yielded an elegant model linking genetic, molecular, cellular, and systems approaches.
Source: ORBi (University of Liège)
Institution: University of Liège
Language: English
Topic: Williams Syndrome Research
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2271163109