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.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) represents one of the most common neurodevelopmental disorders with onset in early childhood, high heritability and documented brain abnormalities [1]
It is known that the variable number of tandem repeats (VNTR) in the 3’untranslated region (3’UTR) of DAT may influence the variability in the therapeutic response to MPH in individuals with ADHD [19, 80]
Therapy with MPH in children with ADHD is accompanied by improvements in attentional and executive dysfunction
Summary
Attention-deficit/hyperactivity disorder (ADHD) represents one of the most common neurodevelopmental disorders with onset in early childhood, high heritability and documented brain abnormalities [1]. Other researches have reported a better response to MPH in patients with the 10/10 genotype and/or 9/10 genotypes compared to subjects with the 9/9 genotype [18, 19], and recent evidence has shown higher striatal DAT concentrations in subjects homozygous for the 10/10 genotype [18]. This narrative review addresses the following aspects: 1) MPH impact on attention and executive functions (EFs) in ADHD; 2) the relation between MPH efficacy and DAT polymorphism; and 3) the role of MPH as an epigenetic modulator in ADHD. We decided to perform a narrative review because our aim was to focus on precision medicine approaches and available studies did not permit to reach this goal with a systematic review
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