Journal
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
Volume 56, Issue 5, Pages 436-444Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jaac.2017.02.009
Keywords
rs945270; putamen; attention-deficit/hyperactivity disorder; reward anticipation; response control
Categories
Funding
- European Union [LSHM-CT-2007-037286, 602450, 602805, 603016]
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- Medical Research Council grant Developmental Pathways Into Adolescent Substance Abuse [93558]
- Medical Research Council grant Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA) [MR/N000390/1]
- Swedish funding agency VR
- Swedish funding agency FORTE
- Swedish funding agency FORMAS
- Medical Research Council
- Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge)
- National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
- Bundesministeriumfur Bildung und Forschung (BMBF) [01GS08152, 01EV0711, eMED SysAlc01ZX1311A]
- Bundesministeriumfur Bildung und Forschung (Forschungsnetz AERIAL)
- Deutsche Forschungsgemeinschaft (DFG) [SM 80/7-1, SM 80/7-2, SFB 940/1]
- National Institutes of Health (NIH), Bethesda, MD (Axon, Testosterone and Mental Health during Adolescence) [RO1 MH085772-01A1]
- NIH Consortium grant [U54 EB020403]
- NIH
- MRC [MR/N000390/1, G0901858] Funding Source: UKRI
- Medical Research Council [MR/N000390/1, G0901858] Funding Source: researchfish
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Objective: In a recent genomewide association study of subcortical brain volumes, a common genetic variation at rs945270 was identified as having the strongest effect on putamen volume, a brain measurement linked to familial risk for attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270 might be a genetic determinant of ADHD, its effects on ADHDrelated symptoms and neural mechanisms of ADHD, such as response inhibition and reward sensitivity, were explored. Method: A large population sample of 1,834 14-year-old adolescents was used to test the effects of rs945270 on ADHD symptoms assessed through the Strengths and Difficulties Questionnaire and region-of-interest analyses of putamen activation by functional magnetic resonance imaging using the stop signal and monetary incentive delay tasks, assessing response inhibition and reward sensitivity, respectively. Results: There was a significant link between rs945270 and ADHD symptom scores, with the C allele associated with lower symptom scores, most notably hyperactivity. In addition, there were sex-specific effects of this variant on the brain. In boys, the C allele was associated with lower putamen activity during successful response inhibition, a brain response that was not associated with ADHD symptoms. In girls, putamen activation during reward anticipation increased with the number of C alleles, most significantly in the right putamen. Remarkably, right putamen activation during reward anticipation tended to negatively correlate with ADHD symptoms. Conclusion: These results indicate that rs945270 might contribute to the genetic risk of ADHD partly through its effects on hyperactivity and reward processing in girls.
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