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Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system

Molecular Psychiatry volume 20, pages 727–734 (2015)Cite this article

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Abstract

Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70–1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22–2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.

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Acknowledgements

This work was supported through funding from the National Institute of Mental Health (5R01MH100286–02). Dr Perlis is supported by NIMH R01MH086026 and by the Stanley Center for Psychiatric Research. The i2b2 platform (PI: Kohane) is supported by award number 2U54LM008748 from the NIH/National Library of Medicine. We express our gratitude to the staff at the Massachusetts Registry of Vital Records and Statistics including Kevin Foster and Dean DiMartino.

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Authors and Affiliations

  1. Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA

    C C Clements, V M Castro, S R Blumenthal, H R Rosenfield, A E Doyle, E B Robinson & R H Perlis

  2. Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA

    C C Clements, S R Blumenthal, H R Rosenfield, A E Doyle, J W Smoller & R H Perlis

  3. Partners Research Computing, Partners HealthCare System, One Constitution Center, Boston, MA, USA,

    V M Castro & S N Murphy

  4. Laboratory of Computer Science and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA,

    V M Castro & S N Murphy

  5. Department of Psychiatry, Depression Clinic and Research Program, Massachusetts General Hospital, Boston, MA, USA,

    M Fava

  6. Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA,

    J L Erb

  7. Information Systems, Partners HealthCare System, New Research Building, Boston, MA, USA,

    S E Churchill

  8. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA,

    A J Kaimal

  9. Analytic and Translational Genomics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA,

    E B Robinson

  10. Department of Medicine, Brigham and Women’s Hospital, New Research Building, Boston, MA, USA,

    I S Kohane

Authors
  1. C C Clements
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  2. V M Castro
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  3. S R Blumenthal
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  4. H R Rosenfield
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  5. S N Murphy
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  6. M Fava
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  7. J L Erb
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  8. S E Churchill
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  9. A J Kaimal
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  10. A E Doyle
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  11. E B Robinson
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  12. J W Smoller
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  13. I S Kohane
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  14. R H Perlis
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Corresponding author

Correspondence to R H Perlis.

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Competing interests

Dr Perlis has received consulting fees or served on scientific advisory boards for Genomind, Healthrageous, Pamlab, Perfect Health, Pfizer, Proteus Biomedical, Psybrain and RIDventures, and received patent fees/royalties from Concordant Rater Systems (now UBC/Medco).

Dr Smoller is a member of the Scientific Advisory Board of Psybrain, Inc.

Dr Fava reports the following: Research Support: Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., Wyeth-Ayerst Laboratories. Advisory/Consulting: Aspect Medical Systems, Astra-Zeneca, Bayer AG, Biovail Pharmaceuticals, Inc., BrainCells, Inc. Bristol-Myers Squibb Company, Cephalon, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithkline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lundbeck, MedAvante, Inc., Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Wyeth-Ayerst Laboratories. Speaking: Astra-Zeneca, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Novartis, Organon Inc., Pfizer Inc, PharmaStar, Wyeth-Ayerst Laboratories. Equity Holdings: Compellis, MedAvante. Royalty/patent, other income: none.

The remaining authors declare no conflict of interests.

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Clements, C., Castro, V., Blumenthal, S. et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 20, 727–734 (2015). https://doi.org/10.1038/mp.2014.90

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