Impact of a Common Genetic Variation Associated With Putamen Volume on Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder

J Am Acad Child Adolesc Psychiatry. 2017 May;56(5):436-444.e4. doi: 10.1016/j.jaac.2017.02.009. Epub 2017 Mar 8.


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 ADHD-related 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.

Keywords: attention-deficit/hyperactivity disorder; putamen; response control; reward anticipation; rs945270.

MeSH terms

  • Adolescent
  • Alleles*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Cross-Sectional Studies
  • Female
  • Genetic Variation*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Motivation
  • Psychiatric Status Rating Scales
  • Putamen / diagnostic imaging
  • Putamen / pathology*
  • Reward
  • Risk Factors
  • Sex Factors
  • Surveys and Questionnaires