Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD

Psychol Med. 2015 Oct;45(14):3009-17. doi: 10.1017/S003329171500094X. Epub 2015 May 28.

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD.

Method: In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated.

Results: A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions.

Conclusions: Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

Keywords: Attention deficit hyperactivity disorder; brain imaging; gene–environment interaction; neuropsychology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Brain / pathology*
  • Child
  • DNA Methylation*
  • Female
  • Gene-Environment Interaction
  • Genotype
  • Humans
  • Hyperkinesis / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Promoter Regions, Genetic
  • Psychiatric Status Rating Scales
  • Republic of Korea
  • Serotonin Plasma Membrane Transport Proteins / genetics*

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins