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Tuesday, April 27, 2004

ADHD - A New Understanding 

You should read Bryan's post titled TV and Attention Deficit--who would've guessed? for a few laughs. Then read the rest of this post.

Last summer, I attended the conference of the American College Health Association. I was able to attend a presentation by Dr. James Ward entitled The Neurobiology of Dyslexia and ADHD. Dr. Ward is a pediatric pathologist who works on referral cases from the College of Charleston Student Health Center. His main work has been in diagnosis of pediatric cases but has worked over the last decade with college students.

Most of the new information comes from knowledge gained through the brain bank and the human genome projects. The brain bank is what the name indicates. A grant was awarded to a medical center/teaching school to collect brains from bodies donated to science. The brains have been carefully studied and you will understand as read where the information comes into play. The human genome projects (there are two major efforts and several smaller projects) have begun to unravel genetics. You will understand when the information is relevant.

The rest of the information has been accepted science for many years and serves to fill in the gaps.

For the last 15 years, one question has halted our understanding of the ADD or ADHD. The causes ADD or ADHD have not been known. We have had several drugs available but have not really known why they worked. We have observed the symptoms of ADD and ADHD. We know how to treat the symptoms, but we have not been so close to a cure as we are now. No, I am not saying the cure is next. However, we are definitely much closer to understanding the cause and that is the last stumbling block to finding a cure.

ADD and ADHD are not actually the same disorder. The APA updates its guidelines for diagnosing a disorder (the book is the referred to as the DSM) as necessary. In the latest edition, ADHD is the main disorder and ADD is a under that umbrella. In the past, ADD was the main disorder and ADHD was a variant. ADD is attention deficit disorder and ADHD is attention deficit and hyperactivity disorder. I will use ADHD from this point forward.

ADHD is a disorder of degree or magnitude. An individual may have a slight case or a really problematic case. The disorder may make one person appear a little absent minded while another person may have major problems in school and work. The deciding factor is genetic. ADHD results from polygenic inheritance. The term polygenic means many genes. You are probably familiar with single gene traits. Hair and eye color are single gene traits. The alleles from your mother and father form a pair to decide your eye color. In one pairing, the result is confirmed. Boom, you've got it. Polygenic inheritance comes into play with traits that are a matter of degree. Intelligence and body shape are examples of polygenic traits. An individual may be a genius, really smart, smart, average, less than average, dumb, or so on. It is not a pairing of one gene code that determines intelligence. Multiple genes must fall into place to determine an individual's inherent intelligence. Similarly, ADHD is polygenic. As the genes fall into place, a child may have a full-blown case or no symptoms at all. It is part of the randomness of life.

Polygenic inheritance is not oblivious to family traits. Yes, some families have a problem with ADHD while others do not. Although genes are random, previous genetic encoding influences genetic inheritance. You may have a family history of polygenic inheritance that you understood as my father's family is tall or my mother's family is smart. That is a history of polygenic inheritance. ADHD may follow a family at the genetic level.

If you have forgotten biology, try to remember that there are 23 paired genes/chromosomes in the human karotype. Only one pair (23rd) determines sex of the child (XX or XY). The other 22 pairs carry basically identical information. Pairs 5 and 11 have been identified as ADHD markers. Pair 4 is possibly involved as well as the X chromosome. The X chromosome is actually a culprit in many genetic disorders that affect boys more than girls. Girls (XX) may have the genetic markers for ADHD on one X chromosome but not on the other X chromosome. The good X counteracts the bad X and we generally see fewer X-linked disorders in girls. Boys (XY), however, have only one X chromosome. They do not have the possibility of having a good X to counteract the markers and are therefore more likely to have the disorder.

You may remember that the brain is divided into two hemispheres (left and right). The left brain handles factual work while the right brain handles creative work. The relationship has been characterized as the left brain is an accountant and the right brain is an artist. The corpus callosum is the part of the brain that allows an individual to switch between hemispheres. In women, the corpus callosum is larger. We have the generalized observations that women can multitask while men can better focus on one thing. A larger corpus callosum means an individual is crossing between hemispheres of the brain more readily. However, a smaller corpus callosum allows an individual to focus in one hemisphere. In the general population, men have a higher potential for spatial math (geometry, calculus, linear algebra), which is a right brain function because of the ability to focus in one hemisphere and the decreased ability to switch. General mathematics is a left brain function and there is no difference in ability between males and females.

In ADHD brains, the corpus callosum is abnormal. The result is that girls are not able to switch hemispheres as readily as their gender peers and boys are not able to change focus as readily as their gender peers. The effect is rather serious. As adults interact with children, especially teachers with students, the interactions are based on expected norms of behavior. When a young girl cannot readily verbally interact or a young boy cannot readily focus on a new subject-project-issue, the adult will begin to accumulate a list of observations that may imply a problem. Too many studies have been substantiated that a teacher's impression of a student may have substantial consequences on the child's performance.

Another anomaly of the brain is glial scarring. Glial cells are brain matter. The human brain is made up of gray and white matter. The gray matter forms an insulating layer around the white matter. This process is myelinization. As neural connections form, myelin forms around the connections to insulate and improve neural transmission. In prenatal development, the gray matter must migrate towards the outer surfaces of the brain through the white matter. Maternal and fetal hormones drive the cell migration in the 8th week of gestation. Any imbalance in the hormone level (especially a reduced amount of estrogen) will cause a flaw in the migration. Estrogen aids the migration of cells. Again, males are at greater risk. However, females with ADHD may have a family history of autoimmune disorders. Glial scarring is the evidence of the flawed migration, then there are two possibilities. Within certain brain formations, two cell types work in balance. Magno and parvo cells work in the auditory cortex and the optic chiasm. Magno cells are rapid transmission cells and parvo cells are slow/deliberate cells. Both are needed for the various functions of the brain parts. When a deficiency exists in the number or function of these cells, the brain part suffers a loss of functioning ability. Especially in dyslexics, a decrease in magno (rapid transfer) cells results in the loss of auditory transfer ability. In the extreme, these individuals may be exempted from spoken foreign languages (college curriculum). If an imbalance occurs in the optic chiasm, an individual may be exempted from spatial math (college curriculum). The term comorbidity is used to state the likelihood of having a related disorder if one disorder is diagnosed. The comorbidity of ADHD with learning disorders is 70%. As you can scaringglial scarring causes ADHD, then the likelihood of having a learning disorder associated with the auditory cortex or optic chiasm is great. In the population of Tourette's syndrome, the comorbidity of ADHD and LD is 50%.

A further anomaly of the brain is a decreased size of the cerebellum of individuals with ADHD. The cerebellum has been overlooked in previous research due to a flawed understanding of its primary function. In the past, scientist thought the cerebellum was an extension of the brain stem in that it ran reflexive functions. Now, research findings indicate that the cerebellum is actually much more involved in high order cognition. For now, the decreased size of the cerebellum in ADHD brains is being studied.

The neurochemistry of ADHD is now readily understood and has driven the introduction of improved drugs. There are two systems of neurochemistry in the brain that are important to ADHD: dopaminergic and noradrenergic. Dopamine is probably a term you have heard of and is essential to the functioning of the brain. A reduction in dopamine is the critical symptom of Parkinson's disease. Norepinephrine (also called noradrenaline) may be familiar to anyone allergic to bee stings. It triggers vasoconstriction and increased heart rate, blood pressure, and blood sugar level. It is the primary component of the injection given to an individual having an allergic reaction. In the brain, dopamine enhances neurological signals and improves attention (focus, on-task behavior, and on-task cognition). Norepinephrine dampens noise, improves executive operations, and increases inhibition. If you look at the list of functions these two agents manage, you will understand immediately the relationship to ADHD: enhanced neurological signals, improved attention (focus, on-task behavior, and on-task cognition), dampened noise, improved executive operations, and increased inhibition.

Drugs used in the treatment of ADHD vary in effect. The drugs fall into three categories: those that stimulate one system, the other system, or both systems. The symptoms of the disorder basically dictate which drug will work most effectively. For about 10 years, Adderall has been explained as a drug similar to Ritalin. Simply, that is wrong. Ritalin (MPH) stimulates the dopaminergic system which in the appropriate dosage produces an enhanced ability to focus and pay attention. However, it does not stimulate the noradrenergic system, which would have blocked outside stimulus and increased inhibition. Adderall stimulates both systems. A new drug, Stratera, has been used as an anti-anxiety drug but has been found to stimulate the noradrenergic system.

However, several factors must be considered when drugs are prescribed. Ritalin and traditional Adderall are easily abused. Ritalin is the #1 abused prescription drug among adolescents and is gaining in popularity among college students. Abuse has two basic forms: academic and recreational. Ritalin will increase the focus of any individual and has developed the reputation of being a study drug. Especially around exam periods, Ritalin is taken by individuals to increase their ability to study. Recreational abuse is a more dangerous form of abuse. Ritalin slowly enters the blood stream when digested. However, when crushed and inhaled the effect of Ritalin is identical to cocaine. Emergency rooms across the nation are reporting increasing numbers of overdose cases involving ADHD drugs (especially Ritalin). Adderall in traditional form can be abused in the same manner as Ritalin. Fortunately, the makers of Adderall have developed a pellet form of the drug, which cannot be easily abused. The traditional Adderall could be crushed and inhaled. A second variant of the pill could not be crushed so individuals would place Adderall in water and after a long period of immersion, would drink the water. This became known as an Adderall cocktail. The latest form of Adderall is a pellet that cannot be crushed or immersed. The only significant problem with Adderall is that it is a 12 hour drug. For college students the problem is more significant. If an individual takes the Adderall early in the morning to attend early classes, the effect will have worn off by the evening when study would occur. Because Adderall stimulates both systems, an individual cannot take another pill to study at night because they would be unable to go to sleep.

How bad are the symptoms? Again, ADHD is a problem of degree. If drugs are prescribed, then dosage must be closely monitored for the appropriate degree of intervention. Further, Dr. Ward concurred with every other expert I have heard or read on the matter of diagnosis. Diagnosis of ADHD is not for general practice MDs and teachers. A full psychometric battery must be administered by competent experts in pediatric practice. If the symptoms are severe enough to impact life, then drug intervention is necessary.

If a child is diagnosed early in life, then the Orton-Gillingham educational intervention may be used. Orton-Gillingham is a multi-sensory, kinesthetic, and tactile stimulation program that uses movement and activity paired to engrain memory. If ADHD is diagnosed too late in life, this intervention is of no use. The problem inherent is early or late diagnosis is that the symptoms of ADHD are not readily distinguished from childhood precocious behavior. Is a child being silly or is the child unable to focus?

I hope that the information is helpful. ADHD is a hard disorder to evaluate because the children appear normal. Often, false attributions or labels are given to the children. Some adults refer to the children as absent-minded, willful, silly, forgetful, day-dreamer, stubborn, etc... When medical evidence is provided, we can begin to accept ADHD as a true disorder. Glial scarring, development of the corpus callosum, size of the cerebellum and neurochemistry are hard science evidence of a disorder. When I speak to undergraduates about medication and ADHD, I use the analogy of insulin. If your child required insulin injections to fight off diabetes and death, would you administer the injections or would you run the risk of your child's death? With ADHD, if the symptoms are severe to the degree that medication is required, then medication is required.

Now that medical science has closed in on the physical manifestation of ADHD, we can assume that very soon work will start on better treatment and possible cures.

I have another soap box devoted to the misdiagnosis of ADHD and the pathology of education for young boys. That is a separate issue. For this ballyhoo, I assume ADHD is an accurate diagnosis.

If you want to learn more, I have some suggestions for reading. Also you can contact Dr. Ward. His contact information from the conference directory is:

James Ward, MD
College of Charleston
Charleston, SC


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