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Download fileOxytocin and Vasopressin Are Dysregulated in Williams Syndrome, a Genetic Disorder Affecting Social Behavior
journal contribution
posted on 2013-10-25, 00:00 authored by Li Dai, C. Sue Carter, Jian Ying, Ursula Bellugi, Hossein Pournajafi-Nazarloo, Julie R. KorenbergThe 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.
Funding
This work was supported by National Institutes of Health (NIH) P01 HD33113, the McDonnell Foundation (Dr. Bellugi, Dr. Korenberg) and NIH MH072935 (Dr. Carter).
History
Publisher Statement
2012 Dai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0038513.Publisher
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