Content area
Abstract
Prader-Willi Syndrome (PWS) is a neurogenetic disorder that occurs in 1 in approximately 20,000 and is the leading cause of genetic obesity. Individuals with PWS present with an array of maladaptive behaviors and compared to others with intellectual disabilities, are more apt to show compulsive behaviors. The features of PWS intuitively suggest hypothalamic and hypothalamic-pituitary-adrenal axis (HPAA) dysfunction. Previous PWS studies have confirmed hypothalamic dysfunction of hormone secretions and hormone-producing neurons, and we address if PWS and the behavioral profile typical of individuals with PWS is associated with alterations in the secretions of oxytocin (OT), vasopressin (VP), and cortisol. OT, VP and cortisol in peripheral plasma were measured using enzyme immunoassay in 21 subjects with PWS (12 females, 9 males) and in 30 normal non-obese control subjects (16 females, 14 males) at a single time point. Behavioral assessments included the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Achenbach Child Behavioral Checklist (CBCL), the Reiss Personality Profiles and a Hyperphagia Questionnaire. Plasma OT (P<0.05) and plasma VP (P<0.05) were elevated in individuals with PWS after logarithmically transforming the data when compared to normal control subjects, and this effect was sex-specific, with males with PWS having increased oxytocin compared to females (P<0.05). In males with PWS, there were significant negative correlations between VP and maladaptive (P<0.05) and food behaviors (P<0.05). In females with PWS there were significant negative correlations between cortisol and maladaptive behaviors (P< 0.01). There were positive correlations in females between OT and obsessive and compulsive behaviors (P<0.05) and one aspect of affiliative behaviors (P<0.01). In female control subjects, OT correlated positively with externalizing behaviors, somatic complaints, anxiety, attention and aggression (P<0.05), while VP correlated positively with sexuality (P<0.05), and cortisol correlated positively with independence (P<0.05). In male control subjects, cortisol correlated positively with anxiety and a sum of maladaptive behaviors (P<0.05), while VP correlated positively with food (P<0.05). These data provide support for hypothalamic dysfunction in PWS. The associations between OT, VP, and cortisol and maladaptive, food-related, and obsessive and compulsive symptomatology in PWS warrant further investigation.