Salivary Melatonin as a Biomarker for Response to Sleep Interventions in Children with Autism
University of Colorado, Denver
Sleep disruption is common among children with autism spectrum disorders (ASD) and represent a significant clinical challenge for treatment. Melatonin is a naturally occurring hormone associated with sleep initiation. Melatonin begins to rise prior to sleep onset. Dim light melatonin onset (DLMO) sampling has been used to document phase advances or delays in the melatonin circadian rhythm associated with sleep disorders. Children with ASD have shown evidence of lower melatonin as well as suggestions of disrupted melatonin synthesis pathways. Melatonin has also been used to treat insomnia in children with ASD without evidence for a disruption in the diurnal melatonin rhythm of the child being treated. However, simple minimally invasive approaches to assessing melatonin in children with ASD are significantly lacking and have relied largely on blood sampling or overnight urine collection. The research team has developed a unique means for saliva collection for several steroids such as cortisol and DHEA using specially adapted filter papers contained in a small collection booklet. These booklets are simple to use and have been successful in distant collaborations ranging from mothers in China to crew on international space station. The research team has successfully used this approach for measuring diurnal salivary cortisol in children with ASD. The study aims to validate this approach for assessing melatonin. In addition, feasibility in a population of children with ASD will be tested in anticipation of a clinical trial of melatonin that would examine DLMO as a predictor of response to treatment. The investigators hope to reliably collect saliva samples using their filter paper collection approach and importantly prove that filter paper collection will be relatively noninvasive from the child's perspective. This project has high relevance to several priority areas of Autism Speaks: novel detection methods (minimally invasive saliva collection), development of a screening approach (DLMO using melatonin collected in saliva samples), and laying the ground work for a larger randomized trial of melatonin to treat insomnia in children with ASD (i.e., those showing delayed onset of melatonin increases at bedtime might respond to a small dose earlier in the day). This is a highly innovative approach to a crucial need among children with ASD that will lead to a randomized melatonin trial based on evaluation of the nocturnal increase in salivary melatonin.