Modafinil and Neurology of Attention Deficit Disorder

It was discovered that ADHD was the result of a deficiency in norepinephrine and that drugs that increase norepinephrine levels relieve the symptoms of ADHD.

That is how Ritalin and other popular ADHD drugs such as Strattera, Adderall or Provigil work. Ritalin and Adderall make the brain produce more epinephrine and Strattera is a selective norepinephrine inhibitor (which means it prevents norepinephrine from being taken up by nerve synapses).

About 70% of people with ADHD respond to stimulants like Ritalin. In the synthesis of norepinephrine, the molecule dopa is converted to dopamine, which is then converted to norepinephrine. Low dopamine levels would cause low norepinephrine levels, which would cause ADHD. Serotonin has also been suggested to play a part in ADHD, albeit in a lesser role.

It is probable that ADHD involves several pathways in the brain which interact and communicate with each other. These would include the frontal and prefrontal areas (which affect attention and impulse control), the limbic system (which regulates emotions), the basal ganglia (which routes information) and the reticular activating system (which affects attention, impulses, and motivation). It is likely that a deficiency in a neurotransmitter in one area would affect others.

Studies have found that there were two brain regions that were smaller in people with ADHD than in people without the disorder. As much as a 10% decrease in volume was found in the frontal lobes and the basal ganglia. The anterior superior regions, such as the right prefrontal lobe and striatal regions, and the globus pallidus and caudate (2 of the 3 functionally significant regions of the basal ganglia) showed smaller volumes and there was abnormal right-left frontal asymmetry in people with ADHD.

I initially took half a pill of Modafinil. Three days later, I took the whole tablet. A week later, it was necessary to take more. But when I had a break and a good rest, it was enough for me to take half a pill again to stay awake during the day.

These brain areas are the ones that regulate attention. The right prefrontal cortex is involved in self-awareness and in resisting distractions. The globus pallidus and caudate nucleus switch off automatic responses as well as coordinating neurological input from many places in the cortex. These areas of the brain also affect the operation of working memory, the internalization of self-directed speech, and the control of emotions and motivation. They allow a person to avoid distractions, recall goals, and take the necessary steps to reach them.

There are also differences in the activity of these regions. PET scans have shown an underactive left anterior frontal region in people with ADHD. SPECT scans have also shown a decreased blood flow in the striatal and frontal regions in the brains of people with ADHD, also suggesting compromised brain activity in those regions.

Studies have suggested that the dopamine D4 receptor gene is linked to ADHD. In mice, when this gene is knocked out, it leads to increased production of dopamine in the caudate nucleus. A mutation of this gene seems to cause “novelty seeking” and is significantly higher in ADHD groups. This mutation when created in cultured cells, results in decreased sensitivity of the receptor to dopamine.

It is even possible that dopamine could malfunction presynaptically in one region and postsynaptically in another. There can be deficits and excesses of dopamine in different brain regions simultaneously. Overactivity in one region may lead to the motor excess and underactivity in another may lead to the cognitive symptoms we see. One neurotransmitter could be having completely opposite effects in different parts of the brain

ADHD is certainly a very complex disorder. I have read that it is like snowflakes in that no two cases are exactly alike. It seems that the closer researchers have looked at it the more complicated the problem of what causes ADHD has become.