Several converging lines of evidence implicate serotonin signaling systems in autism, and 25-30% of autistic individuals show increased platelet serotonin. This is one of the most heritable aspects of autism. We have developed a cellular model system using lymphoblasts prepared from both high-serotonin and normal-serotonin autistic subjects, and intend to exploit this system to determine differences in serotonin signaling in the two groups. We are particularly interested in 5HT1, 2, 6 and 7 receptor signaling and the serotonin transporter, and these lymphoblasts express all of these receptor types. We will determine the relationship between the two groups (as well as cells from normal controls) in terms of serotonin receptor signaling. Since fluorescent fusion proteins have been developed for each of the G proteins that couple to these receptors, variations in cellular localization of these proteins and response to serotonin will be closely monitored. Since these cell lines can also be treated, chronically, with various drugs used in the treatment of autism, we hope to develop a cellular model to predict therapeutic response in Autism and Autism spectrum disorders.
Dr. Mark Rasenick