Interaction Between Maternal 5-HTT Genotype and Prenatal Stress Exposure, Confirmation in Two Independent Samples

Background:  Recent studies suggest prenatal psychosocial stressors during specific prenatal epochs increase the risk of autism. Absence of a 44bp segment of the serotonin transporter gene (5-HTT) promoter region is related to stress responsivity, and has inconsistently been associated with autism. If maternal presence of at least one copy this stress-associated short allele (S-allele) of 5-HTT increases risk of autism with prenatal stress exposure, one would expect the prenatal stress exposure in autism to be more frequently observed in mothers with the S-allele.

Objectives:  Examine the interaction between maternal 5-HTT genotype and prenatal stress exposure in autism.

Methods:  Sixty mothers of children with autism at University of Missouri, and 99 at Queen's University were genotyped, accompanied by surveys regarding prenatal psychosocial stress exposure, and timing of these stressors, as with our previous work. Stress exposure incidence was compared between mothers carrying the S-allele and mothers lacking the S-allele using Chi-square, performed separately for the previously reported critical window of months 5-6 of gestation, and for the entire pregnancy.

Results:  For both samples, stress exposure during months 5-6 of gestation was significantly higher among mothers with the S-allele (Missouri-p=0007, Queen's-p=0.037), with no relationship for the entire pregnancy (p=0.13) for Missouri, but a significant relationship for the entire pregnancy (0.018) for Queen's. To determine whether the maternal S-allele might increase recall of prenatal stress, the stress surveys were also completed for unaffected siblings pregnancies. Reported stress exposure was not higher in S-allele mothers for unaffected sibling pregnancies.

Conclusions:  These data suggest that maternal genotype for stress susceptibility genes is a critical factor in the effect of prenatal stress exposure on autism. Further understanding of the mechanism may eventually allow the possibility of prevention in some cases.