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Simplex and Multiplex Stratification in ASD and ADHD Families: A Promising Approach for Identifying Overlapping and Unique Underpinnings of ASD and ADHD?

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Abstract

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are highly heterogeneous neuropsychiatric disorders, that frequently co-occur. This study examined whether stratification into single-incidence (SPX) and multi-incidence (MPX) is helpful in (a) parsing heterogeneity and (b) detecting overlapping and unique underpinnings of the disorders. ASD and ADHD traits were measured in 56 ASD/31 ADHD SPX families, 59 ASD/171 ADHD MPX families and 203 control families. In ASD but not ADHD, behavioral traits were less elevated in SPX than MPX unaffected relatives, suggesting that SPX–MPX stratification may thus help parse ASD, but not ADHD heterogeneity. Particularly unaffected relatives from MPX ASD/ADHD families displayed elevated trait levels of both disorders, indicating shared (multifactorial) underpinnings underlying ASD and ADHD in these families. Cross-disorder traits were highest in MPX ASD unaffected siblings.

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Acknowledgments

We would like to thank parents, teachers and children participating in this study. We also thank Saskia W. de Ruiter and all interns for their assistance with data collection. This study was partly funded by a grant assigned to N. Rommelse by the Netherlands Organisation for Scientific Research (NWO Grant No. 91610024); a grant assigned to S. Faraone by the National Institute of Mental Health (NIH Grant No. R01 MH62873-01A1); and by a grant assigned to J. Buitelaar by the Netherlands Organization for Scientific Research (NWO Grant No. 1750102007010).

Conflict of interest

J.K. Buitelaar has been a consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, Organon/Shering Plough, UCB, Shire, Medice, Roche and Servier. All other authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands

    Barbara Franke & Nanda N. J. Rommelse

  2. Karakter, Child and Adolescent Psychiatry University Centre Nijmegen, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands

    Anoek M. Oerlemans, Yvette G. E. De Bruijn, Daphne J. Van Steijn, Jan K. Buitelaar & Nanda N. J. Rommelse

  3. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Catharina A. Hartman

  4. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands

    Anoek M. Oerlemans, Yvette G. E. De Bruijn & Jan K. Buitelaar

  5. Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands

    Barbara Franke

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  1. Anoek M. Oerlemans
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  2. Catharina A. Hartman
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Correspondence to Anoek M. Oerlemans.

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Oerlemans, A.M., Hartman, C.A., De Bruijn, Y.G.E. et al. Simplex and Multiplex Stratification in ASD and ADHD Families: A Promising Approach for Identifying Overlapping and Unique Underpinnings of ASD and ADHD?. J Autism Dev Disord 45, 645–657 (2015). https://doi.org/10.1007/s10803-014-2220-9

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