Prenatal Interaction Between Genotype and Stress in the Development of Autism Spectrum Disorder

Background:  

While genetics has been shown to have a strong influence in the etiology of Autism Spectrum Disorder (ASD), other factors must also contribute to this disorder.  Our previous research has shown a significant increase in prenatal stress in mothers of children with ASD with a peak at weeks 21-32 of gestation.  However, not all mothers that encounter stressful situations during pregnancy have children with ASD.  It is possible that genetics may play a role in stress tolerance in the development of ASD.  The serotonergic system holds particular interest in this regard.  The serotonergic system has been implicated as a possible contributing factor to the development of ASD.  Moreover, an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTT) gene, SLC6A4, has been associated with anxiety and stress reactivity, and some studies have suggested an association with ASD in carriers of the short allele.

Objectives:  

Our aim is to discover if this polymorphism found in the serotonin transporter gene may interact with environmental stressors to produce a higher risk for the development of ASD in the child.  This study, to our knowledge, is the first to look at this novel gene and stress interaction on the etiology of ASD.

Methods:  

Blood was collected from families with children diagnosed with ASD for genetic analysis.  DNA was isolated using Flexigene (Qiagen, Valencia, CA) kit following manufacturer specifications.  PCR was performed using previously documented protocol.  Mothers were asked to complete several questionnaires regarding their history of stress exposure during pregnancy, and the timing of the stressors.

Results:  

Early evidence suggests that mothers with the 5-HTTLPR short allele have higher numbers of stressors and stressor severity during pregnancy, predominantly during the critical period of pregnancy identified in our previous work, when compared to carriers of the long allele.

Conclusions:  

This study is beginning to suggest a gene and environment interaction in the development of ASD.  Our study continues to show the significance of stress during gestation in the etiology of ASD particularly during weeks 21-32.  More importantly, this evidence further identifies a specific potential gene that appears to interact with prenatal stress exposure in association with this risk.  Future studies will be needed for further understanding of how environmental factors interact with genetics in autism, and exploration of ways to mitigate this risk.