Interaction between seratonin transporter genotype and prenatal stress on neurodevelopment with implications for autism spectrum disorder

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Prenatal stress has been shown to have a profound and lasting impact on brain development. Stress exposure during pregnancy has been implicated in several psychiatric conditions, including autism spectrum disorder (ASD). Previous research has shown that prenatal stress increases the risk for ASD with a peak exposure period occurring during months five and six of the pregnancy. The present studies examined a maternal genetic variation in the serotonin transporter gene affecting stress tolerance and its interaction with environmental stressors on the increased risk for ASD. Furthermore, embryonic brain development was investigated in an animal model of this gene and stress interaction to explore its effects on early brain developmental processes. Mothers of children with autism completed questionnaires regarding the prenatal environment and donated blood samples for genetic testing at the University of Missouri and Queen's University for converging evidence from two independent samples. Mothers carrying the stress susceptible variant of the serotonin transporter gene experienced a greater number of stressors and stress severity when compared to mothers carrying the long allele variant. Importantly, the temporal peak occurrence of stressors in these mothers was consistent with previous findings. When exploring the effects of this gene and environment interaction on early neurodevelopmental processes in mice, the GABAergic system showed clear disturbances in proper development. Identification of these early born GABAergic cells revealed aberrant distribution of cells migrating from through the brain. These data are consistent in showing the detrimental and long lasting effects of prenatal stress on the developing brain. Furthermore, prenatal stress shows a more profound effect on neurodevelopment when paired with a maternal genetic susceptibility to stress potentially leading to more severe outcomes such as autism spectrum disorder.