ADHD Pathophysiology

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By Yolanda Smith, B.Pharm.Reviewed by Afsaneh Khetrapal, BSc

The exact pathophysiology of Attention Deficit Hyperactivity Disorder (ADHD) is not clear. With this said, several mechanisms have been proposed as factors associated with the condition. These include abnormalities in the functioning of neurotransmitters, brain structure and cognitive function.

Although it remains unknown if these mechanisms cause or are consequences of the condition, they appear to be linked to the pathophysiology of ADHD and are evident in affected individuals. Their possible roles are discussed in more detail below.

Neurotransmitters

Due to the efficacy of medications such as psychostimulants and noradrenergic tricyclics in the treatment of ADHD, neurotransmitters such as dopamine and noradrenaline have been suggested as key players in the pathophysiology of ADHD.

These medications work to reduce the symptoms of ADHD by helping to facilitate the release and function of the dopamine or noradrenaline neurotransmitters. For this reason, a deficiency in neural transmission may be linked to the pathophysiology and symptoms of ADHD.

Other research based on adults with ADHD has also supported the theory of involvement of neurotransmitters. Depressed dopamine activity has been associated with the condition, and has been identified in affected individuals with the use of positive electron transmission (PET) scans.

Brain Structure

The frontal and prefrontal regions of the brain, as well as possibly the parietal lobe and cerebellum, are thought to be associated with ADHD. These structural areas have been identified with magnetic resonance imaging (MRI), as some research has shown that children with ADHD tended to have altered activation of the brain when performing certain tasks.

Deformations of the basal ganglia nuclei in children with ADHD may also be involved. In general, children with more severe deformations tend to have worse symptoms. This theory may be supported by the efficacy of stimulant drugs in treating ADHD, which may help to reduce the deformations.

Additionally, some research has shown that children who are more hyperactive or impulsive have a slower rate of cortical thinning in the brain, which is most evident in the prefrontal regions of the brain. This is characteristic of ADHD throughout adolescence.

Cognitive Function

ADHD is also linked to some neurophysiological deficits and abnormalities in cognitive function. These deficits may usually be seen in the resting brain but the Default-Mode-Network (DMN) activity may be involved, which is key in the region of the brain used to process tasks. As a result, affected individuals are likely to have difficulty in regulating and maintaining attention.

Cognitive top-down executive control is thought to help monitor memory, cognitive flexibility and inhibition. This is particularly important when individuals are performing complex tasks that have high adaptation and effort demands.

Abnormalities in the function of this system may be seen in patients with ADHD and lead to the symptoms characteristic of the condition. This may include slow or variable reaction times when performing certain tasks and an increase in the number of errors made.