Kuntsi, Jonna; Wood, A. C.; Rijsdijk, Frühling; Johnson, K. A.; Andreou, Penny; Albrecht, B.; Arias-Vasquez, Alejandro; Buitelaar, Jan K; Mcloughlin, G.; Rommelse, Nanda N.J.; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.S.; Uebel, Henrik; van der Meere, Jaap; Banaschewski, Tobias; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Royers, H.; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Asherson, Philip:

Separation of cognitive impairments in attention deficit hyperactivity disorder into two familial factors

In: Archives of general psychiatry, Jg. 67 (2010) ; Nr. 11, S. 1159-1166
ISSN: 0003-990X
Zeitschriftenaufsatz / Fach: Medizin
Context Attention deficit hyperactivity disorder (ADHD) is associated with widespread cognitive
impairments, but it is not known whether the apparent multiple impairments share etiological
roots, or whether separate etiological pathways exist. A better understanding of the etiological
pathways is important for the development of targeted interventions and for identification of
suitable intermediate phenotypes for molecular genetic investigations.
Objective To determine, using a multivariate familial factor analysis approach, whether one or
more familial factors underlie the slow and variable reaction times (RTs), impaired response
inhibition, sustained attention, and choice impulsivity that are associated with ADHD.
Design An ADHD and control sibling-pair design.
Setting Belgium, Germany, Ireland, Israel, Spain, Switzerland and the United Kingdom.
Participants The sample consisted of 1265 participants, aged 6 to 18 years: 464 probands with
ADHD and 456 of their siblings (524 with ADHD combined subtype), and 345 control participants.
Main Outcome Measures Performance on a four-choice RT task, a go/no-go inhibition task and a
choice-delay task.
Results The final model consisted of two familial factors. The larger factor, reflecting 85% of the
familial variance of ADHD, captured 98-100% of the familial influences on mean RT and RT
variability. The second smaller factor, reflecting 12.5% of the familial variance of ADHD, captured
62-82% of the familial influences on commission and omission errors on the go/no-go task. Choice
impulsivity was excluded in the final model, due to poor fit.
Conclusions The findings suggest the existence of two familial pathways to cognitive impairments
in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The
familial distinction between the two cognitive impairments is consistent with recent theoretical
models – a developmental model and an arousal-attention model – on two separable underlying
processes in ADHD. Future research that tests the familial model within a developmental
framework may inform developmentally-sensitive interventions.