Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors.
BACKGROUND
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 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, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD.


METHODS
An ADHD and control sibling-pair design.


METHODS
Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom.


METHODS
A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants.


METHODS
Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task.


RESULTS
The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit.


CONCLUSIONS
The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom. jonna.kuntsi@kcl.ac.uk
Jonna
J
Kuntsi
Alexis C
AC
Wood
Frühling
F
Rijsdijk
Katherine A
KA
Johnson
Penelope
P
Andreou
Björn
B
Albrecht
Alejandro
A
Arias-Vasquez
Jan K
JK
Buitelaar
Gráinne
G
McLoughlin
Nanda N J
NN
Rommelse
Joseph A
JA
Sergeant
Edmund J
EJ
Sonuga-Barke
Henrik
H
Uebel
Jaap J
JJ
van der Meere
Tobias
T
Banaschewski
Michael
M
Gill
Iris
I
Manor
Ana
A
Miranda
Fernando
F
Mulas
Robert D
RD
Oades
Herbert
H
Roeyers
Aribert
A
Rothenberger
Hans-Christoph
HC
Steinhausen
Stephen V
SV
Faraone
Philip
P
Asherson
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002755:Choice Behavior / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005163:Factor Analysis, Statistical; D005190:Family; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D010375:Pedigree; D010641:Phenotype; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D035781:Siblings