New Insights on the Effects of Methylphenidate in Attention Deficit Hyperactivity Disorder

Abstract

This narrative review describes an overview of the multiple effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) and its potential neurobiological targets. It addressed the following aspects: 1) MPH effects on attention and executive functions in ADHD; 2) the relation between MPH efficacy and dopamine transporter gene (DAT) polymorphism; and 3) the role of MPH as an epigenetic modulator in ADHD. Literature analysis showed that MPH, the most commonly used psychostimulant in the therapy of ADHD, acts on multiple components of the disorder. Marked improvements in attentional and executive dysfunction have been observed in children with ADHD during treatment with MPH, as well as reductions in neurological soft signs. MPH efficacy may be influenced by polymorphisms in the DAT, and better responses to treatment were associated with the 10/10 genotype. Innovative lines of research have suggested that ADHD etiopathogenesis and its neuropsychological phenotypes also depend on the expression levels of human endogenous retrovirus (HERV). In particular, several studies have revealed that ADHD is associated with HERV-H over-expression and that MPH administration results in decreased expression levels of this retroviral family and a reduction in the main symptoms of the disorder. In conclusion, there is a confirmed role for MPH as an elective drug in the therapy of ADHD alone or in association with behavioral therapy. Its effectiveness can vary based on DAT polymorphisms and can act as a modulator of HERV-H gene expression, pointing to targets for a precision medicine approach.

Effect of short-term methylphenidate on social impairment in children with attention deficit/hyperactivity disorder: systematic review

“…It is expected that MPH would improve momentary processes in children with ADHD, namely, the encoding of emotional inputs or the ability to control actions. Indeed, reports by parents and teachers suggest that children treated with MPH show improvement in social interactions and a reduction in oppositional or aggressive behavior at home and in the classroom [ 51 ]. However, it is unclear whether MPH treatment also affects long-term acquisition of social behaviors, and thus the overall social performance of children with ADHD.…”

The Moderating Role of Emotional Regulation on the Relationship between School Results and Personal Characteristics of Pupils with Attention Deficit/Hyperactivity Disorder

“…In the literature, executive functions are seen as a top-down process and are defined as the abilities that allow the planning and organization of information in working memory and behavioral self-regulation in such a way that the behavioral response is adapted to the dynamic context in which the person is [ 11 ]. Meanwhile, emotion regulation is seen as a bottom-up process, and represents the ability of an individual to modify an emotional state in order to achieve adaptive, goal-oriented behaviors [ 12 ].…”

Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies

“…Dopaminergic neurotransmission is involved in brain functions including reward system, motor control and emotion regulation [ 26 ]. The efficacy of dopamine neurotransmission stimulants in mitigating ADHD suggests that the normal dopaminergic neurotransmission may have been disrupted in ADHD patients [ 27 ]. Dopamine synthesis takes several steps, among which tyrosine hydroxylase (TH) is the rate-limiting enzyme to produce dopamine ( Fig.…”