17685
Association Between a Polymorphism in the Maternal Serotonin Transporter Gene and Prenatal Stress and a Subset of ASD with Hypersensitivity to Sensory Stimuli
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with a highly heterogeneous phenotype. Identifying subsets of ASD and their possible causes is a critical step in creating a more complete understanding of the disorder and may provide insight into potential treatments. Dysfunction in the serotonergic system has been implicated in the etiology of ASD. Evidence in animal models and preliminary data in humans in our lab suggests that a maternal polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) interacts with prenatal stress to cause an increased risk for the development of ASD in the child. Knockout of the serotonin transporter has shown the critical role of this gene in the proper development of the sensory barrel fields in the rodent brain. Since a portion of individuals with ASD have extreme hypersensitivity to sensory stimuli, it is of interest to investigate the possible association between the maternal 5-HTTLPR polymorphism and prenatal stress, both of which have profound effects on the serotonergic system, and this abnormal sensory phenotype in the ASD population.
Objectives:
Our aim is to discover if children with ASD exposed to prenatal stress with a mother carrying the short allele in the promoter region of the serotonin transporter gene are more prone to have hypersensitivity to sensory stimuli.
Methods:
Blood was collected from families with children diagnosed with ASD for genetic analysis. DNA was isolated using a Flexigene (Qiagen, Valencia, CA) kit following manufacturer specifications. PCR was performed using previously documented protocols. Products were then analyzed via gel electrophoresis. Mothers were asked to complete several questionnaires regarding their history of stress exposure during pregnancy, and the timing of the stressors. Additionally, forms describing detailed information on the child’s sensitivity to visual and auditory stimuli were filled out by the parents.
Results:
Early evidence suggests that a maternal 44 base-pair deletion in the 5-HTTLPR interacts with prenatal stressors to increase the risk for a subset of ASD with hypersensitivity to sensory stimuli. These children were more likely to be reported as having severe discomfort and negative reactions to either visual or auditory stimuli or both compared to children with ASD not exposed to these factors.
Conclusions:
This study is beginning to suggest a specific gene and environment interaction during development may increase the risk for a particular subset of ASD. More data is needed and is still being collected in this study. However, these preliminary results provide insight into a distinct mechanism underlying a specific behavioral phenotype observed in this neurodevelopmental condition.