Prader-Willi syndrome (PWS) has long been characterized by hyperphagia, food obsessions, and increased risks of obesity in affected individuals. Although less well-described, many people with PWS show obsessions and compulsions not related to food, as well as significant behavioral dysfunction. The proposed study will examine these obsessions, compulsions, and other maladaptive features, filling a long-standing behavioral research void in this complex developmental disorder. To this aim, the investigators propose to identify the onset, course, and phenomenology of obsessive-compulsive symptoms in PWS, and how these relate to children with obsessive-compulsive disorder (OCD). PWS is hypothesized to represent a specific clinical subtype of OCD, opening up possible roles for genomic imprinting or the PWS Critical Region in delineating these subtypes. It is hypothesized that compulsivity in PWS has an unusually early-onset, and that salient features of the PWS cognitive-behavioral phenotype may provide new clues into how compulsivity is expressed in young children. Early-onset compulsivity is also likely associated with aspects of hyperphagia and of normative development.
The second aim i s to identify possible mechanisms in PWS that mediate the expression of compulsivity. The proposed study hypothesizes that whole-blood serotonin will mediate symptom expression, and that subtle differences in symptoms may be seen across PWS subjects with paternally-derived deletions at 15q11-q13 versus those with maternal uniparental disomy of chromosome 15. Third, the investigators aim to determine the distinctiveness of compulsivity in PWS relative to children with Williams syndrome (WS), and Down syndrome (DS). WS is a particularly powerful contrast group as it is characterized by increased anxiety and obsessional thinking. The three aims will be addressed in two ways: 1) a longitudinal study of 60 children with PWS, WS, and DS aged 2 to 7 years who are tested twice, two years apart; and 2) a cross-sectional study of 35 children with PWS aged 10-14 years who are compared to subjects with WS, DS, and appropriately matched children with OCD. Findings will shed new light on treatment, on certain subtypes of OCD, and on the range and correlates of PWS' complex behavioral phenotype.
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