Journal of Autism and Developmental Disorders

, Volume 47, Issue 11, pp 3489–3496 | Cite as

Interactive Effects of Prenatal Antidepressant Exposure and Likely Gene Disrupting Mutations on the Severity of Autism Spectrum Disorder

  • Sean Ackerman
  • Sarah Schoenbrun
  • Caitlin Hudac
  • Raphael Bernier
Original Paper


To examine the interactive effects of two proposed risk factors which may contribute to symptom severity of Autism Spectrum Disorder (ASD): prenatal antidepressant exposure and likely gene-disrupting (LGD) mutations. Participants included 2748 individuals with ASD from the Simons Simplex Collection. We examined the effects of prenatal antidepressant exposure, maternal depression, presence of an LGD mutation and their interaction on ASD severity. We found a significant interactive effect between antidepressant exposure and the presence of an LGD mutation on ASD severity in the ADOS and ADI-R verbal communication domains. We consider a “two-hit” model in which one variable lays the foundation for an initial risk which is compounded by a second variable.


Autism ASD Antidepressants SSRI Genetics 



We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base.

Author contributions

SA participated in study design and coordination, and drafted the manuscript; SS participated in the interpretation of the data and the early manuscript drafts; CH performed the statistical analysis; RB conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript.


This work was supported by a grant from the Simons Foundation (SFARI #89368) and from the National Institute of Mental Health (#01MH100047 to R.B.). This study was funded by the Medical Student Research Training Program (MSRTP), University of Washington School of Medicine, Seattle, WA. The funding source did not participate in any part of the performance of the study.

Compliance with Ethical Standards

Conflict of interest

All authors report no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sean Ackerman
    • 1
  • Sarah Schoenbrun
    • 2
  • Caitlin Hudac
    • 3
  • Raphael Bernier
    • 4
  1. 1.Department of Psychiatry, Child & Adolescent PsychiatrySSM Dean Medical GroupMadisonUSA
  2. 2.School of MedicineUniversity of WashingtonSeattleUSA
  3. 3.Department of PsychiatryUniversity of WashingtonSeattleUSA
  4. 4.Department of Psychiatry and Center on Human Development and DisabilityUniversity of WashingtonSeattleUSA

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