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The World Federation of ADHD Guide 87 levels and which are thought to underpin ADHD. As described by the inverted U-shaped curve mentioned above, both too little and too much DA and NA re- sult in sub-optimal cognitive functioning and are implicated the development of side-effects and impairments. ADHD is associated with lower levels of DA and NA; but too much DA is thought to be a key cause of psychotic symptoms, and excessive NA can lead to anxiety, agitation or aggression. A key aim of medication treatment is to optimise neurotransmission through the important, predominantly glutamatergic, brain circuits, which function sub-optimally in ADHD. These me- dications correct the levels of DA and NA, which modulate and correct the subop- timal glutamatergic transmissions. Whilst there are similarities between the medications, there are also key dif- ferences. This is the reason why some people respond better to one medication than another (and also why some have adverse effects with one and not another). Methylphenidate and the amphetamines inhibit both the dopamine (DAT) and noradrenaline reuptake transporters. These transporters’ function is to remove DA and NA from the synaptic and extra synaptic spaces. Blocking reuptake, in- creases the amount of available DA and NA, that engages dopamine (D1) re- ceptors, thereby improving neurotransmission by reducing the amount of ‘noise’ and interference (DA) and boosting the ‘signal’ (NA). Atomoxetine only inhibits the noradrenaline reuptake transporter, however it also increases levels of both NA and DA in the prefrontal cortex (because in the prefrontal cortex, almost all Figure 5.1 The inverted U-shaped influence of noradrenaline (NA) and dopamine (DA) on prefrontal cortex. Cognitive performance Optimal Too little Too much