Obsessions On a Biomarker: Serotonin Genetics in Autism

The most persistent biomarker in autism is the phenomenon of elevated serotonin in ~30% of individuals with autism. This has been repeatedly observed and found to be a heritable trait. Because of this and other evidence, scientists have long speculated a role for serotonin in the genetic underpinnings of autism. Recent observations of rare serotonin transporter (SERT) mutations in autism families supports this “serotonin hypothesis”. These mutations, also found in families segregating Asperger syndrome, OCD and other neuropsychiatric phenotypes, result in a gain-of-function to SERT leading to elevated transporter activity. Other studies identified a common coding variant (Leu33Pro) in the integrin β3 gene (ITGB3) as influencing circulating serotonin levels and associating with autism risk. We now understand that ITGB3, which physically associates with SERT, alters SERT activity and regulation in an allele-specific manner and does so both peripherally and centrally. While SERT is a key player in regulation of serotonin signaling, it is only one node in a broader network of molecules that regulate serotonin. In this session, we will review findings from autism genetic studies that touch broadly on serotonin biology.