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.