The Effects of COMT Polymorphism on Cortical Thickness and Surface Area Abnormalities in Children with ADHD

Cereb Cortex. 2019 Aug 14;29(9):3902-3911. doi: 10.1093/cercor/bhy269.


The catechol-O-methyltransferase (COMT) gene is associated with frontal cortex development and the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, how the COMT gene impacts brain structure and behavior in ADHD remains unknown. In the present study, we identify the effect of COMT on cortical thickness and surface area in children with ADHD and children with typically developing (TD) using a machine learning approach. In a sample of 39 children with ADHD and 34 age- and IQ-matched TD children, we found that cortical thickness and surface area differences were predominantly observed in the frontal cortex. Furthermore, a path analysis revealed that a COMT genotype affected abnormal development of the frontal cortex in terms of both cortical thickness and surface area and was associated with working memory changes in children with ADHD. Our study confirms that the role of COMT in ADHD is not restricted to the development of behavior but may also affect the cortical thickness and surface area. Thus, our findings may help to improve the understanding of the neuroanatomic basis for the relationship between the COMT genotype and ADHD pathogenesis.

Keywords: attention-deficit/hyperactivity disorder (ADHD); catechol-O-methyltransferase (COMT); cortical thickness; machine learning; surface area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / pathology*
  • Catechol O-Methyltransferase / genetics*
  • Cerebral Cortex / pathology*
  • Child
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Polymorphism, Single Nucleotide


  • COMT protein, human
  • Catechol O-Methyltransferase