title: Cognitive impairments are different in single-incidence and multi-incidence ADHD families.
abstract: BACKGROUND
  We may improve our understanding of the role of common versus unique risk factors in attention-deficit/hyperactivity disorder (ADHD) by examining ADHD-related cognitive deficits in single- (SPX), and multi-incidence (MPX) families. Given that individuals from multiplex (MPX) families are likely to share genetic vulnerability for the disorder, whereas simplex (SPX) ADHD may be the result of sporadic (non-)genetic causes unique to the patient, we hypothesized that cognitive impairments may be different in SPX and MPX ADHD as indicated by (a) the presence of cognitive deficits in MPX, but not SPX unaffected siblings and (b) dissimilar cognitive profiles in SPX and MPX ADHD patients.
  
  
  METHODS
  Tasks measuring total IQ, verbal attention, executive functioning, motor functioning, and time estimation were administered to 31 SPX/264 MPX ADHD probands, 47 SPX/123 MPX unaffected siblings, and 263 controls, aged 6-19 years.
  
  
  RESULTS
  SPX unaffected siblings were unimpaired compared to controls, except for verbal working memory, whereas MPX unaffected siblings showed impairments on most cognitive domains. The cognitive profiles of SPX and MPX probands were highly similar, except that verbal attention, response inhibition and motor control deficits were more pronounced in MPX probands, and -compared to their unaffected siblings- impairments in IQ, visual working memory and timing abilities were more pronounced in SPX cases.
  
  
  CONCLUSIONS
  Our results support the hypothesis that a partly different cognitive architecture may underlie SPX and MPX forms of ADHD, which becomes evident when contrasting cognitive performances within families. Cognitive factors underlying MPX forms of ADHD are familial, whereas nonfamilial in SPX ADHD. SPX-MPX stratification may be a step forward in unraveling diverse causal pathways.
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Karakter, Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
authors.forename: Anoek M
authors.initials: AM
authors.lastname: Oerlemans
authors.affiliation: Department of Psychiatry, University of Groningen, Groningen, The Netherlands.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: Karakter, Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.|Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Yvette G E
authors.initials: YGE
authors.lastname: de Bruijn
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Karakter, Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.|Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Karakter, Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
authors.forename: Nanda N J
authors.initials: NNJ
authors.lastname: Rommelse
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D058068:Endophenotypes; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011594:Psychometrics; D012307:Risk Factors; D055815:Young Adult
keywords: Attention-Deficit/Hyperactivity Disorder (ADHD); endophenotype; family; simplex-multiplex stratification; unaffected relative