Autism Spectrum Disorders (ASDs) are complex neurodevelopmental disorders that occur in approximately 1 in 68 children today, an increase from 1 in 2,000 just 50 years ago. The causes of ASD are unknown, but a growing body of evidence supports a critical role for both genetic and environmental factors, particularly during gestation and the early postnatal period. Among numerous environmental exposures that have increased in prevalence over the past decades is perinatal exposure to antidepressant medications, which are currently used by 7%-13% of pregnant women in the United States. In the first study to examine risk of autism following prenatal exposure to antidepressants, we found a significant 3-fold increased risk associated with first trimester SSRI exposure. Subsequent studies in other populations have reported increased risk of ASD associated with in utero exposure to SSRIs, although not all studies have found such evidence. The interpretation of these collective findings is limited by exposure and outcome misclassification and confounding by indication, and lack of integration of underlying genetic susceptibility. The proposed study will overcome these limitations by utilizing data and biospecimens already collected in the SEED study (Study to Explore Early Development, www.cdc.gov/ ncbddd/autism/caddre.html), the largest, multi-site, population-based case- control study of autism in the United States. We will explore main and joint effects of maternal antidepressant use, maternal psychiatric disease history, and maternal and child genetic susceptibility. We seek funds to generate genome-wide SNP data and perform targeted genotyping on 1608 SEED mothers and to support analyses of these perinatal environmental, maternal and child genetic, and ASD phenotypic data to 1) examine the effect of perinatal exposure to SSRI antidepressants on risk of ASD; 2) evaluate the role of perinatal SSRI exposure in ASD risk in the context of maternal mental health status; and 3) examine whether perinatal SSRI exposure and child or maternal genotype interact to impact risk of ASD. This study leverages the extensive data already assembled by SEED, which provide comprehensive information on several important confounders not previously measured, robust and valid measurement of child phenotype, genome-wide SNP data on children, and maternal genetic samples. Since SEED data collection focused on the preconception through early postnatal period, the proposed study has the ability to identify developmental time periods of greatest vulnerability to SSRI exposure and aid clinicians and mothers in making informed decisions about the management of perinatal depression. Our study may identify specific maternal or child profiles that indicate heightened susceptibility to perinatal SSRI exposure and shed light on potential biological mechanisms underlying ASD development. Finally, since early life exposure to antidepressants is common and modifiable, the proposed research has the potential to make a large public health impact and guide research targeting ASD interventions and therapies.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
