Methylation levels of the serotonin transporter gene (SLC6A4) promoter region correlate with behavioural symptoms of ADHD in children and associated neurobiological factors, report preliminary findings from a recent South Korean study.
The aim of this study was to ascertain whether SLC6A4 methylation patterns are associated with clinical characteristics and regional brain cortical thickness in children with ADHD. Children with ADHD (n=102; aged 6–15 years) were assessed using the K-SADS-PL*, the ADHD Rating Scale-IV and computerised continuous performance tests, in order to measure ADHD core and related symptoms. Quantitative DNA methylation analysis was performed using blood samples to assess the methylation status of the SLC6A4 gene; and whole brain structural magnetic resonance imaging was utilised to measure brain cortical thickness.
Results identified statistically significant links between the methylation levels of the SLC6A4 gene promoter region and symptoms of ADHD. After adjusting for age, sex and IQ: higher methylation status in the CpG6 and CpG8 regions of SLC6A4 were associated with higher hyperactivity/impulsivity symptom scores; CpG4 and CpG5 with higher total ADHD Rating Scale scores; and CpG6, CpG7 and CpG8 with more commission errors. Mean average methylation levels in the SLC6A4 promoter region overall were associated with higher hyperactive-impulsive scores, higher total ADHD Rating Scale scores and more commission error scores. Furthermore, methylation levels in the CpG5, CpG6, CpG7 and CpG8 regions demonstrated negative correlation with cortical thickness levels in the right occipito-temporal brain regions.
These preliminary data point to a link between increased methylation status of the SLC6A4 promoter region and hyperactivity and impulsivity symptoms. Increased promoter methylation is associated with decreased gene activity, and the current study indicates that over-methylation of the promoter in question in children with ADHD reduces serotonin synthesis, which may have a resulting effect of increased hyperactivity and impulsivity. The researchers also suggest that the lack of serotonin may alter structural brain development. However, further research is warranted to confirm these findings, given the small sample group and lack of control group present in this study.
Read more about the role of SLC6A4 methylation in ADHD here
*Kiddie-Schedule for Affective Disorders and Schizophrenia – Present and Lifetime
Park S, Lee JM, Kim JW, et al. Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD. Psychol Med 2015: 45: 3009-3017.