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BERKSHIRE AD/HD RESEARCH GROUP DNA-RESEARCH PROJECT

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Dopamine neurons run through regions of the brain that regulate attention and impulse control. Because Dopamine helps us regulate attention, a disruption in the Dopamine system results in trouble organizing thoughts, paying attention, and feeling connected. For sometime, people treating AD/HD wondered why the drug Ritalin, a stimulant, would help hyperactive children become less stimulated the answer lies in the cascade theory. Dopamine converts into norepinephrine. AD/HD involves an underutilization of Dopamine and norepinephrine. Drugs that act on serotonin act on Dopamine and norepinephrine. The cascade involving these three neurotransmitters is the key to AD/HD.

When there is a short supply of neurotransmitters that inhibit incoming stimuli, too many signals get through and cause overload. This may be the genetic link between AD/HD and compulsive disorders such as substance use disorders and gambling. Sufferers of AD/HD are more vulnerable to addiction than other people, not just because they are looking for a way to relieve their discomfort but because something different happens when they use a mood altering substance or behavior.

Reward Deficiency Gene:

Researchers in the USA found that the brain wave called P300 (or P3) was much smaller in the sons of alcoholic fathers than comparable waves in the sons of nonalcoholic fathers. The importance of this information is that it gives strong evidence that children of alcoholics have unique characteristics that are genetically, not environmental, determined.

With the accumulation of evidence overwhelmingly pointing to the genetic factor scientists looked for a gene or a set of genes that could be identified as the causative factor. Each individual has one hundred thousand genes and a billion pairs of DNA stored in twenty three chromosomes. In a system this complex, how could a researcher hope to fine a gene or a group of genes responsible?

Drs Kenneth Blum and Ernest Noble decided to tackle the problem they had one simplifying factor studies of the reward cascade had shown that neurotransmitters such as serotonin, Dopamine, GABA, and opioids are almost certainly involved in generating feelings of well being or craving. Craving is a key factor in addiction.

Dr Nobles' large collection of frozen brains of individuals who had died of severe alcoholism and a group of brains from nonalcoholics were used for comparison. The history of each alcoholic brain was known in clinical detail. Tissues from these brains provided ideal sources of DNA for studying both genes and receptors, making it possible to investigate not only suspect genes but any associated impairment of receptor functions well.

Scientists made connection with the Dopamine D2 receptor gene the results were dramatic. There are two variants of the Dopamine D2 gene, called the Al allele and the A2 allele. After testing DNA from the total sample, including both alcoholics and nonalcoholics, they found that 69% of the alcoholics HAD the Al allele and 31% did not. Of the nonalcoholics 80% did NOT have the Al allele, while 20% did.

This discovery indicated a strong association between this variant of the gene and the severe form a alcoholism. This does not prove that the Al allele of the Dopamine D2 receptor gene is the single cause of this type of alcoholism, but it is a powerful indication that it is involved or associated with it. The presence of the Al allele of the Dopamine D2 receptor gene is a predisposing gene - if you have it you are at high risk of developing alcoholism or some other compulsive or impulsive disorder which includes AD/HD.

The lack of Dopamine receptors in individuals who are deficient in the Al allele may have an important bearing on their inability to cope with stress. Dopamine is known to reduce stress, and if there is a shortage of Dopamine receptors, stress reduction does not happen. Alcohol, cocaine, marijuana, nicotine, and carbohydrates are substances that can cause such a release of Dopamine in the brain, thereby bringing about a temporary relief. They can be used singly, in combination or interchangeably.

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