Introduction. Prader-Willi syndrome (PWS) is characterized by obesity, hypotonia, hypogonadism, hyperphagia, short stature, and a neurobehavioral profile that includes cognitive deficits, learning problems, and behavioral difficulties that increase in both quantity and severity over time. PWS results from an alteration in the molecular composition of a critical region of C#15q. Morbid obesity resulting from hyperphagia is amplified by decreased energy expenditure and reduced physical activity. The hyperphagia has proven refractory to all psychopharmocologic intervention; the behavioral components are equally resistant to psychotropic intervention. PWS patients’ body composition resembles that of individuals with growth hormone (GH) deficiency, including short stature and reduced lean body mass with concomitant increased fat mass. We hypothesized that GH administration to children with PWS, in addition to stimulating linear growth, would improve body composition, increase energy expenditure and fat utilization, and improve muscle strength, physical agility, and pulmonary function. Two recent reports from this study document significant positive effects of GH treatment on these children’s physical parameters measured in a 2-year, controlled study. However, the behavioral impact of GH treatment in this population remains incompletely described.A psychosocial burden, including emotional, behavioral, and cognitive disturbances associated with short stature, has been previously described in a non-PWS population with GH deficiency and idiopathic short stature. An impaired quality of life and psychosocial status is also documented in otherwise normal adults with GH deficiency. In both populations, growth hormone replacement therapy (GHRT) is reported to improve alertness, activity level, endurance, irritability, tendency to worry, and extroversion resulting in better personal relationships with fewer conflicts. This report focuses on that portion of the study investigating the behavioral and psychosocial outcomes accompanying increased stature and improved physical status for persons with PWS treated with GHRT. We hypothesized that, as in other populations, GHRT for persons with PWS would have a significant positive effect on their psychosocial status as well as an improvement in their growth parameters.Methods. A 2-year, controlled study with control group crossover in the second year was used. Fifty-four consecutive children with genetically confirmed PWS were enrolled. Patients were 4 to 16 years of age at time of enrollment, had skeletal maturation 13 for girls and 15 for boys; all but 3 participants remained prepubertal (Tanner stage 1) throughout the study. Children who had previous therapy with GH were excluded, as were children with a scoliosis 20°. After a 6-month growth assessment were randomized into a 60:40 treatment:control ratio. Treatment consisted of Nutropin (Genentech), 1 mg/m2/day.A modified Offord Survey Diagnostic Instrument (SDI) was used to monitor behavior at 6-month intervals. The SDI is a 165-item behavioral checklist with items rated on a scale of 0 = Never or Not True, 1 = Sometimes or Somewhat True, and 2 = Often or Very True. The items are balanced between positively and negatively scored items. The present instrument was designed to derive diagnoses for the following Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition categories: Depression, Obsessive-Compulsive Disorder, Anxiety Disorder, Somatization Disorder, Conduct Disorder, and Attention-Deficit/Hyperactivity Disorder. The SDI was modified to include 10 items specifically inquiring about PWS (eg, denies having PWS, picks excessively at skin, nose, or other body parts). Because diagnoses are not mutually exclusive, an individual can meet criteria for 1 or more diagnostic categories.The SDI contains a second section measuring behavior functioning in the school environment, in the family, and in personal and social relationships. A wider scoring range is used and is question-specific. Parallel forms of this measure are available for parents, teachers, and the child him/herself. We gathered data from both parents and teachers at 6-month intervals. No questionnaire was scored until the completion of the entire study to avoid any possibility of an inadvertent “feedback” or “self-fulfilling prophecy” effect. All questionnaires were scored by a Bachelor’s level research assistant blind to study assignment.Family stress was monitored with the Family Inventory of Life Events. At study completion, the impact of GH was measured with a 13-item summary interview adapted from Wiren et al. After completion of all final study visits, a single research assistant blind to treatment assignment interviewed all families by phone. This method was chosen to minimize any positively biased demand characteristics.Results. Both between-group and within-group contrasts were computed for baseline, 12 (time 1) and 24 month (time
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