Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition
Publication: American Journal of Psychiatry
Abstract
Objective:
Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates.
Methods:
Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124).
Results:
Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity.
Conclusions:
Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.
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History
Received: 13 December 2013
Revision received: 27 October 2014
Accepted: 3 November 2014
Published online: 23 January 2015
Revision received: 19 May 2015
Published in print: July 01, 2015
Revision received: 22 October 2015
Authors
Author Contributions
Drs. Buitelaar and Hartman contributed equally.
Funding Information
NIH Clinical Center10.13039/100000098: R01MH62873
Supported by NIMH grant R01 MH-62873 (to Dr. Faraone), NWO Large Investment Grant 1750102007010 (to Dr. Buitelaar), and grants from Radboud University Nijmegen Medical Center, from University Medical Center Groningen and Accare, and from VU University Amsterdam.Dr. Hoekstra has received advisory panel payments from Shire as well as an unrestricted research grant from Shire. In the past year, Dr. Faraone received income, travel expenses, and/or research support from and/or has been on an advisory board for Pfizer, Ironshore, Shire, Akili Interactive Labs, CogCubed, Alcobra, VAYA Pharma, Neurovance, Impax, and NeuroLifeSciences and has received research support from the National Institutes of Health (NIH); his institution is seeking a patent for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD; in previous years, he received consulting fees or was on advisory boards or participated in continuing medical education programs sponsored by Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly; and he receives royalties from books published by Guilford Press and Oxford University Press. In the past 3 years, Dr. Oosterlaan has received an investigator-initiated grant from Shire Pharmaceuticals. In the past 3 years, Dr. Buitelaar has been a consultant to, member of an advisory board for, and/or speaker for Janssen Cilag, Eli Lilly, Bristol-Myers Squibb, Shering Plough, UCB, Shire, Novartis, and Servier; he is not an employee of any of these companies and not a stock shareholder of any of these companies; he has received no other financial or material support, including expert testimony, patents, and royalties. All other authors report no financial relationships with commercial interests.Metrics & Citations
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