Many people with Prader-Willi Syndrome (PWS) frequently engage in severe skin picking behavior, often causing open wounds and sores that can become infected. Why do people with PWS do this? How often and under what circumstances does it occur? Are people with PWS more likely to exhibit skin picking when they are bored or anxious? Does the skin picking hurt? Or do individuals with PWS have a high pain tolerance? In other words, is the problem caused by environmental, physiological, or neural factors? As in most disorders, it is crucial to understand the underlying cause of the symptoms because it ultimately helps to identify appropriate treatments. In this research project, we therefore will investigate the possible causes of skin picking in PWS using state-of-the-art behavioral and neuroimaging methods. These methods will help us to develop and implement individualized treatments for this behavior. For example, if we find that for some people, environmental processes are involved in skin picking, behavioral management techniques may be implemented (e.g., if skin picking occurs when the individual is left alone without appropriate competing activities, environmental enrichment may prove useful). If we find that skin picking for some people is associated with aberrant neural processes, pharmacological approaches to treatment may be required (e.g., if skin picking occurs because it activates brain centers that release neurotransmitters, such as endogenous opioids, medications that block or reduce their release may be prescribed). Finally, if we find that for some people, both environmental and neural processes are involved, a combination of behavioral and pharmacological treatments may be required. To our knowledge, this will be the first study to identify the potential causes of skin picking in PWS and will pave the way for new “disease-specific” treatments for this distressing, stigmatizing, and disabling behavior problem in PWS.