Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?
BACKGROUND
Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied.


METHODS
The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose.


RESULTS
Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results.


CONCLUSIONS
In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. doylea@helix.mgh.harvard.edu
Alysa E
AE
Doyle
Stephen V
SV
Faraone
Larry J
LJ
Seidman
Erik G
EG
Willcutt
Joel T
JT
Nigg
Irwin D
ID
Waldman
Bruce F
BF
Pennington
Joanne
J
Peart
Joseph
J
Biederman
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D035843:Biomedical Research; D003071:Cognition; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005824:Genetics, Behavioral; D006801:Humans; D010641:Phenotype