The Role of Epigenetics in the Pathogenesis and Potential Treatment of Attention Deficit Hyperactivity Disorder

Abstract

: There is increasing evidence that dsyregulated epigenetic mechanisms of gene expression are involved in the pathogenesis of attention deficit hyperactivity disorder (ADHD). This review presents a comprehensive summary of the current state of research on the role of epigenetics in the pathogenesis of ADHD. The potential role of epigenetic drugs in the treatment of ADHD is also reviewed. Several studies suggest there are epigenetic abnormalities in preclinical models of ADHD and in ADHD patients. Regarding DNA methylation many studies have reported DNA hypermethylation. There is evidence that there is increased histone deacetylation in ADHD patients. Abnormalities in the expression of microRNAs (miRNAs) in ADHD patients have also been found. Some currently used drugs for treating ADHD, in addition to their more well established mechanisms of action, have been shown to alter epigenetic mechanisms of gene expression. Clinical trials of epigenetic drugs in patients with ADHD are reporting favorable results. These data suggest that abnormal epigenetic mechanisms of gene expression may be involved in the pathogenesis of ADHD. Drugs acting on epigenetic mechanisms may be a potential new class of drugs for treating ADHD.

Effect of lead exposure on histone modifications: A review

“…Moreover Luo et al [ 43 ] reported elevated H3 acetylation in hippocampal regions of offspring which is also involved in the pathophysiology of ADHD. [ 106 ] Similarly Scheider et al [ 41 ] had also reported that Pb exposure along with prenatal stress can result in PTHMs in hippocampal and frontal cortex region in a sex dependent manner. Extensive maternal exposure to Pb during postnatal and lactating periods can also alter the offspring's epigenome via transmission through lactating milk.…”

Polygenic risk score for attention‐deficit/hyperactivity disorder and brain functional networks segregation in a community‐based sample

“…29 Moreover, great advances have been made in uncovering epigenetic mechanisms underlying ADHD development. 30,31 For instance, ADHD-PRS was also shown to be correlated with global and peripheral DNA methylation levels. [32][33][34] Despite such remarkable advances in both genetics and neuroimaging investigations of ADHD, the putative mechanisms by which polygenic architecture influences clinical features via functional neurodevelopment remain largely speculative.…”

“…Interestingly, ADHD‐PRS is also associated not only with hyperactivity/impulsivity symptoms, but also with genetic vulnerability for a myriad of psychiatric symptoms and disorders in children and in the general population 29 . Moreover, great advances have been made in uncovering epigenetic mechanisms underlying ADHD development 30,31 . For instance, ADHD‐PRS was also shown to be correlated with global and peripheral DNA methylation levels 32–34 …”

“… 29 Moreover, great advances have been made in uncovering epigenetic mechanisms underlying ADHD development. 30 , 31 For instance, ADHD‐PRS was also shown to be correlated with global and peripheral DNA methylation levels. 32 , 33 , 34 …”