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Sci Rep. 2018 May 16;8(1):7620. doi: 10.1038/s41598-018-26042-y.

Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

Author information

1
Peking University Sixth Hospital (Institute of Mental Health), National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), 51 Huayuan Bei Road, Beijing, 100191, China.
2
Shenzhen Children's Hospital, 7019 Yitian Road, Shenzhen, 518038, China.
3
CAS Key Laboratory of Mental Health, Institute of Psychology, 16 Lincui Road, Beijing, 100101, China.
4
College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shang Yuan Cun, Beijing, 100044, China.
5
CAS Key Laboratory of Mental Health, Institute of Psychology, 16 Lincui Road, Beijing, 100101, China. changsh@psych.ac.cn.
6
Department of Psychology, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China. changsh@psych.ac.cn.
7
Peking University Sixth Hospital (Institute of Mental Health), National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), 51 Huayuan Bei Road, Beijing, 100191, China. yangli_pkuimh@bjmu.edu.cn.

Abstract

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

PMID:
29769613
PMCID:
PMC5956073
DOI:
10.1038/s41598-018-26042-y
[Indexed for MEDLINE]
Free PMC Article

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