Adult Attention Deficit Hyperactivity Disorder - Pathophysiology


Over the last 30 years, research into ADHD has greatly accelerated. There is no single, unified theory that explains the cause of ADHD and research is ongoing. Genetic and environmental factors are thought to play a part.

It is becoming increasingly accepted that individuals with ADHD have difficulty with what neuropsychologists call "executive functioning." In higher organisms, such as humans, these functions are thought to reside in the frontal lobes. They enable recall of tasks that need accomplishing, organization to accomplish these tasks, assessment of consequences of actions, prioritization of thoughts and actions, keeping track of time, awareness of interactions with surroundings, the ability to focus despite competing stimuli, and adaptation to changing situations. They are also required for the ability to judge what is "right" or "correct" as opposed to what is "wrong" or "incorrect".

Phineas Gage, a railroad worker who in 1848 survived a large iron rod being accidentally driven through his head, is often cited as a demonstration that executive function resides in the frontal lobes, because at least one of those lobes was destroyed in Gage by the accident, after which his behavior and personality were markedly changed. However, while Gage's case certainly stimulated 19th-century thinking about the brain and the localization of its functions, most specific uses of Gage to illustrate theoretical ideas about the brain employ greatly exaggerated descriptions of his behavioral changes.

The executive functions of the brain in the frontal lobes are thought to be linked to the rest of the brain by way of the prefrontal cortex. This part of the brain is involved in working memory and linked to the limbic system, which controls the basic emotions of fear, anger, pleasure and also plays an important role in the formation of long-term memories. The nucleus accumbens is a part of the brain that is involved in the internal reward system and allows the feeling of pleasure, success, or accomplishment in response to certain stimuli. Many of these interconnections are via dopaminergic pathways. For example, cocaine and amphetamines act directly on this part of the brain to stimulate dopamine release, giving users a euphoric feeling.

Several lines of research based on structural and/or functional imaging techniques, stimulant drugs, psychological interventions have identified alterations in the dopaminergic and adrenergic pathways of individuals with ADHD. In particular, areas of the prefrontal cortex appear to be the most affected. Dopamine and norepinephrine are neurotransmitters playing an important role in brain function. The uptake transporters for dopamine and norepinephrine are overly active and clear these neurotransmitters from the synapse a lot faster than in normal individuals. This is thought to increase processing latency, diminishes working memory, and affects salience.

Stimulants, such as methylphenidate and amphetamine act on these neurons to increase the availability of dopamine and norepinephrine for neurotransmission. They act to correct the problem with the "wiring". Methylphenidate acts by blocking the dopamine and norepinephrine transporters, thus slowing the pace at which these neurotransmitters are cleared from the synapse. Amphetamine acts in a similar fashion, but also increases the release of these neurotransmitters into the synaptic cleft by temporarily reversing the uptake process.

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