Our group has previously shown a markedly different time course in the developmental measures of serotoninsynthesis in children with autism as compared to non-autistic children using PET imaging (Funded by NICHDRO1 HD34942). These data are consistent with the notion that serotonin synthesis is abnormal during criticalperiods of brain development in autistic children. Specific to this project, we showed that serotonin synthesiscapacity in children less than the age of 6 years showed significantly lower values than non-autistic children.Since serotonin is known to be an important factor involved in postnatal synaptogenesis, we hypothesized thatone approach to the treatment of core features of autism pharmacologically is the use of serotonin agonists inchildren less than the age of 6 years. The goal of this treatment is to provide a more normal modulation ofsynaptic plasticity in autistic children during the early childhood years. For this study, we chose the 5HT1Aserotonin agonist buspirone. The rationale for the choice of buspirone was based upon basic studiesdemonstrating a prominent role of the 5HT1A receptor in the regulation of postnatal synaptogenesis. Our long-range goal is to utilize neuroimaging markers in autism, which can be used in therational design of treatment in groups or subgroups of children with autism. The goal of this study is to testfurther the safety and efficacy of buspirone in a large group of young children. This trial is guided by pilot studyresults funded by NICHD through the Pediatric Pharmacology Research Unit (PPRU) network. In our pilotstudy, we demonstrated improvement in social interaction, repetitive behavior, sensory dysfunction and anxietywith 3 months of buspirone treatment. A subset of the children continued in a 6-month open label study andshowed further improvement by the end of the open label study. In addition, serotonin synthesis capacitymeasured with alpha[11C]methyl-L-tryptophan (AMT) positron emission tomography (PET) was related to theresponse to buspirone in the pilot study, while plasma serotonin was not. Thus AMT PET will be tested as abiomarker for drug response.
| Chugani, Diane C; Chugani, Harry T; Wiznitzer, Max et al. (2016) Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial. J Pediatr 170:45-53.e1-4 |
