ADHD is linked with disturbances in the function of the central catecholaminergic system and for those reasons; catecholaminergic systems are the main targets of stimulant and non-stimulant medications prescribed to improve ADHD symptoms. A catecholamine is a monoamine neurotransmitter and the most abundant catecholamines in the human body are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine, all of which are produced from the amino acids phenylalanine and tyrosine. The central catecholaminergic system is thought to play an important role in both motor activity and cognition .
A review by Wilens (2008) provides a detailed and comprehensive overview of the effects of methylphenidate on the catecholaminergic system in ADHD and is referenced throughout this section for those that wish to obtain and read the full article. This next section however will provide a brief outline of the main points of the review paper.
Methylphenidate (MPH) has a modulating effect on catecholaminergic tone, impacting the striatum and prefrontal cortex regions of the brain; resulting in improvements in motor hyperactivity, distractibility and attention deficits. Treatment with methylphenidate elevates levels of dopamine (DA) signalling via several actions:
- by blocking the DA reuptake transporter and amplifying the DA response period, most prominently in striatal brain regions.
- creating less inhibition of DA D2 auto-receptors and magnification of DA tone.
- activation of D1 receptors on the postsynaptic neuron .
The performance of MPH in the cortex may also be mediated by stimulation of the noradrenergic α2 receptor and dopamine (DA) D1 receptor. The function of other neurotransmitters such as serotonin, α-agonists, histamine and acetylcholine in regulating catecholamine pathophysiology in ADHD and medication for ADHD are less understood.
Treatment with MPH is estimated to reduce the core symptoms in approximately 70% of children with ADHD [8, 10]. A meta-analysis of placebo-controlled, clinical trials in children has confirmed the efficacy of MPH in improving (1) cognitive abilities, (2) behavioural and academic ratings and (3) inhibition [11, 12]. The most reliable effect of MPH on brain function in children with ADHD is the up-regulation and normalization of decreased frontal and striatal activation [13-16]. Essentially what this means is that impairments previous observed in these brain regions are functionally activated in a comparable way to healthy control children during the administration of MPH.