title: Identifying Unique Versus Shared Pre- and Perinatal Risk Factors for ASD and ADHD Using a Simplex-Multiplex Stratification.
abstract: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Besides shared genetic factors, pre- and perinatal risk factors (PPFs) may determine if ASD, ADHD, or the combination of both disorders becomes manifest. This study aimed to test shared and unique involvement of PPFs for ASD and ADHD, using an approach that stratifies the sample into affected/unaffected offspring and single-incidence (SPX) versus multi-incidence (MPX) families. Pre- perinatal data based on retrospective parent-report were collected in 288 children (71 % males) from 31 SPX and 59 MPX ASD families, 476 children (65 % males) from 31 SPX and 171 MPX ADHD families, and 408 control children (42 % males). Except for large family size and more firstborns amongst affected offspring, no shared PFFs were identified for ASD and ADHD. PPFs predominantly related to ASD (maternal infections and suboptimal condition at birth) were more often reported in affected than unaffected siblings. PPFs associated with ADHD (low parental age, maternal diseases, smoking and stress) were shared between affected and unaffected siblings. Firstborn-ship was more frequent in SPX than MPX ASD probands. Our results suggest that the co-morbidity of ASD and ADHD is not likely explained by shared PPFs. Instead, PPFs might play a crucial role in the developmental pathways leading up to either disorder. PPFs in ADHD appear to index an increased shared risk, whereas in ASD PPFs possibly have a more determining role in the disorder. SPX-MPX stratification detected possible etiological differences in ASD families, but provided no deeper insight in the role of PPFs in ADHD.
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands. anoek.sluiter-oerlemans@radboudumc.nl.|Karakter, Child and Adolescent Psychiatry University Centre, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands. anoek.sluiter-oerlemans@radboudumc.nl.
authors.forename: Anoek M
authors.initials: AM
authors.lastname: Oerlemans
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marlot J
authors.initials: MJ
authors.lastname: Burmanje
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands.|Karakter, Child and Adolescent Psychiatry University Centre, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: Karakter, Child and Adolescent Psychiatry University Centre, Reinier Postlaan 12, 6525 GC, Nijmegen, The Netherlands.|Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Nanda N J
authors.initials: NN
authors.lastname: Rommelse
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D000067877:Autism Spectrum Disorder / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: Attention-Deficit/Hyperactivity Disorder (ADHD); Autism Spectrum Disorders (ASD); Prenatal and perinatal risk factors; Simplex-multiplex stratification