Attention Deficit Hyperactivity Disorder in the Light of the Epigenetic Paradigm

Abstract

Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder characterized by a definite behavioral pattern that might lead to performance problems in the social, educational, or work environments. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of ADHD were restricted to those associated with cognitive (attention deficit) and behavioral (hyperactivity/impulsivity) deficits, while deficient emotional self-regulation, a relevant source of morbidity, was left out. The etiology of it is complex, as its exact causes have not yet been fully elucidated. ADHD seems to arise from a combination of various genetic and environmental factors that alter the developing brain, resulting in structural and functional abnormalities. The aim of this paper was to review epigenetics and ADHD focused on how multidimensional mechanisms influence the behavioral phenotype.

Prenatal unhealthy diet, insulin‐like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early‐onset conduct problems

“…high fat/sugar) is of particular interest as it has been reported to associate with both CP and ADHD (Howard et al., ; Jacka et al., ; Liu, Raine, Venables, & Mednick, ; Sonuga‐Barke et al., ). A potential mechanism that might help explain the link between ‘unhealthy diet’ and CP and ADHD is the epigenetic process of DNA methylation, which is highly responsive to the nutritional environment (Drake et al., ), and also associates with CP‐related phenotypes (Cecil et al., ) and ADHD (Schuch, Utsumi, Costa, Kulikowski, & Muszkat, ; van Mil et al., ; Walton et al., ).…”

Methyl donor supplementation alters cognitive performance and motivation in female offspring from high‐fat diet – fed dams

“…DNA methylation is hypothesized to link the gestational environment with adult disease (12) via persistent changes in gene expression. In autism, schizophrenia, and ADHD, aberrant DNA methylation and methyltransferase function have been implicated in development of these diseases and cognitive dysfunction (13–15). In our mouse model, we have shown that offspring who were exposed to maternal HFD have whole‐genome DNA hypomethylation in multiple brain regions, including the prefrontal cortex (PFC), along with promoter‐specific hypomethylation and dysregulated gene expression (9).…”

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

“…Recently, IGF2 DNA methylation may be as predisposing factor to develop ADHD (33, 54, 55). In fact, prenatal exposure to high-fat and -sugar diet promotes IGF2 DNA methylation at birth that, in turn, has been positively associated with higher ADHD symptoms (28).…”

“…High expression of BDNF is also found in a model of autism [valproic acid (VPA)-treated rat offspring] (54). In addition to the high BDNF expression in hippocampus, the VPA-treated rats show low expression of p-Akt, Bcl-2, p-CaMKII, as well as a significant increase in Bax and caspase-3 expression (33).…”