ADHD: A Precursor to Alcoholism? (Corpus Callosum part 2)

In the previous blog post on ADHD and alcoholism, we investigated some of the signs of overlap between the two disorders. One factor which both disorders appear to share in common is a reduction in volume of specific brain regions, including the corpus callosum, the genu, and the isthmus, when compared to similar individuals who do not exhibit either of the symptoms of ADHD or alcoholism. For a generalized location of these brain regions, please see the diagram below (which is a reprint of the figure from the last blog entry):

The corpus callosum is the tan band located inside of the gyrus cinguli, also known as the cingulate gyrus, a brain region whose role in ADHD we have discussed previously. The isthmus region is relatively small and is not labeled on this diagram. It is located to the right of the label "corpus callosum", and is just to the left of the area labeled "splenium".

**Please note my use of nomenclature here, I am continuing to use the same labeling as I did in the previous post. Here, we are considering the "genu" and "isthmus" as separate, distinct regions from the corpus callosum due, in part, to how they were classified in the studies I have been reviewing. However, many professionals label them all as one entity, with the genu and isthmus serving as sub-sections of the corpus callosum as a whole.

In today's blog, we will discuss the answers to two key questions:

1. Is there a hereditary factor at play for the size abnormalities for these three brain regions?


2. Does the outward expression of symptoms for one of these two disorders predate the other? In other words, is the appearance of ADHD symptoms a warning sign of impending alcohol abuse (or vice versa)?

For the answer to the first question, we turn to a journal article by Venkatasubramanian and coworkers in the journal Psychiatry Research: Neuroimaging. This group found that the relative size of the corpus callosum, genu and isthmus regions of the brain were correlated to an individual being at "high-risk" or "low-risk" for alcohol abuse. In this study, the "high-risk" group had a statistically significant reduction in size of multiple brain regions when compared to the "low-risk" group.

For comparison purposes, the "high-risk" group had approximately:

• a 9% reduction in corpus callosum volume
• a 13% reduction in the volume of the genu, and
• a 17% reduction in isthmus volume when compared to the low-risk group for these brain regions.

**Note: it worth mentioning that the comparative differences in relative brain sizes followed some sort of age-dependent trend. The subjects of study were boys and young men between the ages of 9 and 23. For the age 9-15 group, all three of the above brain regions were smaller. However, for the older group (over 15), only the isthmus region had a statistical size difference between the "high-risk" and "low-risk" groups. This suggests that either the isthmus region follows a much greater developmental delay in individuals identified as being "high-risk" for alcohol dependence than do the corpus callosum or the isthmus region never does fully "catch up" in size to the "low-risk group"

So what exactly constitutes "high" and "low" risk? In this study, the researchers studied males between the ages of 9 and 23 (sampling a relatively even distribution across this age range) who had male parents who both:

1. Developed an alcohol dependence before the age of 25 (average age of dependence around 20)
2. At least two relatives (first-degree), who also had alcohol dependence (average was 3 relatives).

The "low-risk" control group of children and young adults consisted of individuals whose parents were not diagnosed with alcoholism or any other psychological disorders. To ensure that maternal genetic influences were not a factor, none of the mothers of the children (the 9 to 23 year-old group) in the study were diagnosed with alcohol abuse.

This study is of potential interest. While the sample size was small (only 20 "high-risk" and 20 "low-risk"), the choice of following only male parents and male children offered some clear-cut advantages over other similar studies. Among them were:

• It eliminated gender effects. While debatable, some studies have found brain regions like the corpus callosum to be larger in males than in females. Having an all-male study eliminated this potential factor.


• The ages of the two groups (high and low risk) followed similar distribution patterns, to rule out size increases in these brain regions due to aging.


• Since the alcoholism was restricted to the paternal side, physiological effects during pregnancy were eliminated. This is important, as several studies have shown that maternal alcohol consumption during pregnancy can affect the development process including relative sizes of these brain regions. In other words, confounding effects, such as fetal alcohol syndrome were significantly reduced, since none of the mothers in the study suffered from clinical alcohol abuse.


• None of the 9 to 23 year-old test subjects had already developed an alcohol dependence. This eliminates the effects that chronic alcoholism has on reducing the size of the corpus callosum, as reported in recent studies.


• Other than alcoholism for fathers of the "high risk" group, none of the parents of the study participants had any other psychological disorder. This is important, especially due to the effects of comorbidity (disorders or symptoms occurring alongside alcoholism, such as conduct disorders or abuse of other substances) on worsening the symptoms of alcoholism.

So how does ADHD tie in to all of this?

Based on this study's findings, it appears that the expression of ADHD (as well as other "externalizing symptoms", which are symptoms that can be seen outwardly, such as hyper-excitability, conduct disorders, substance abuse, etc.) may be a warning sign of impending alcohol abuse.

For example, it has been postulated that hyperexcitability, which is often seen in individuals with ADHD (especially of the hyperactive-impulsive or combined subtypes) is a genetic precursor to alcohol dependence. In this case, and ADHD-like trait predates alcohol abuse. In other cases, symptoms such as substance abuse, conduct disorders, impulse control problems and other antisocial behaviors have grouped under the umbrella term generalized disinhibitory complex. Here, these numerous symptoms are essentially "clumped together" as one generalized behavior.

Regardless of the "model" one subscribes to, please keep in mind that a reduction in size the corpus callosum, genu and isthmus regions of the brain have been associated with ADHD.

Additionally, the degree of overlap between the two disorders was definitely worth mentioning. Out of the 20 children and young adults of the "high-risk" group, 17 of them were diagnosed with ADHD. Out of the 20 "low-risk" children? Zero.

Keep in mind that the fathers of the high-risk group were not diagnosed with any other disorders, just alcoholism. Additionally, keep in mind that none of the high-risk children had developed an alcohol dependence as of yet. These facts give compelling evidence that fathers who suffer from early-onset alcohol dependence who are not even ADHD themselves, are much more likely to have male children with ADHD, with an onset which precedes alcohol dependence itself.

In essence, this study established a degree of linkage (but not necessarily a direct cause) between the expressed behaviors of ADHD and alcoholism and the physiological features of relative sizes of the isthmus, corpus callosum and genu.

Hopefully this provides evidence that there is in fact a strong underlying hereditary component surrounding both disorders of ADHD and alcoholism. In the next couple of posts, we will investigate some of the individual genes thought to be involved in both of these disorders.

ADHD and Alcoholism: The Corpus Callosum (part 1)

In our last post, we discussed some of the ties between ADHD and eating disorders such as bulimia. In this post, we will begin the first of a multi-part investigation on the connection between ADHD and alcoholism. In this session, we will see how these two disorders are both tied to improper function in a key brain region known as the corpus callosum.

Note the relative position of the corpus callosum in the diagram below (source of image here):

A quick aside: Note the proximity of this corpus callosum brain region to the cingulate gyrus (labeled "Gyrus cinguli" in the diagram above), a region which we discussed in a recent post on attentional control. The cingulate region can be thought of as the brain's "gear shifter". If underactive, it leads to consistent lack of focus on one thought or task (a hallmark characteristic of ADHD), if overactive, the cingulate can result in overfocus (a characteristic of obsessive compulsive disorder, or OCD).

Returning to the corpus callosum area of the brain, which is layered inside the cingulate gyrus, we can see some sub-regions of note. These include the genu and the splenium. There is also a small region (not listed on the diagram above), called the isthmus, which is just to the left of the splenium. Of these regions, pay close attention to the isthmus, genu, and corpus callosum.

Note: the classification of these brain region sometimes varies, some methods classify the isthmus and genu as part of the corpus callosum, while others group them as seperate elements. No need to get any further into specifics, but when I refer to "corpus callosum" in the context of this post, I am referring to the region distinct from the isthmus, genu and splenium.

The corpus callosum is primarily responsible for connecting and integrating information from the left and right hemispheres of the brain. It is composed of millions of individual fibers and is necessary for the integration and processing of sensory information and expressing this information through verbal language. This is one of the later-developing regions of the brain, and continues to develop and become more efficient during adolescence (and even into early adulthood). Studies have shown that this prolonged developmental process leaves brain regions like the corpus callosum more prone to improper development. One of the reasons young children have trouble expressing visual images verbally is because speech control is typically on the left side of the brain and visual imaging and imagination is typically on the right.

Improper development of this corpus callosum region can lead to quirks such as split brain. Additionally, it has been reported that development of this brain region can be impeded by prenatal alcohol exposure and is entirely missing in around seven percent of children with fetal alcohol syndrome. Additionally, chronic alcohol abuse can result in thinning in the corpus callosum region.

In addition to the inhibition of this key brain region due to alcohol exposure listed above, it appears that there may be an underlying factor at play for this region for both ADHD and alcoholism. A reduction in size in the corpus callosum, genu and isthmus has been associated with ADHD in both children and adults. A study done by Venkatasubramanian and coworkers found a connection between smaller volumes in these same three regions of the brain and an increased risk of developing alcoholism.

Note that a reduction in size of the corpus callosum has been linked with a decreased functional ability in this region as well. This includes the processing of information between the left and right hemispheres of the brain in processes such as integrating information of visual images obtained from both eyes.

In addition to its role in expressing and processing ideas and thoughts from both sides of the brain, the corpus callosum is also integral in coordinating movements in different parts of the body. This includes governing motor inhibition (restricting unwanted or inappropriate movements) across the body. Interestingly, individuals with ADHD have been shown to have a decreased ability in utilizing the corpus callosum to control movements, which is often tied to the impulsive behavior of ADHD individuals with their actions (such as constantly grabbing or playing with objects at inappropriate times).

The corpus callosum is not the only brain region thought to be involved with both ADHD and alcoholism. For example, the prefrontal cortex (the brain region behind the forehead), which we have discussed extensively in other posts, has repeatedly been found to be underactive for individuals with ADHD. Additionally, Schweinsburg and coworkers found a decrease in activation of the prefrontal cortex correlates with a higher risk in suffering from alcoholism.

In the next few posts, we will examine some of the genes thought to be underlying factors in both ADHD and alcohol abuse. Additionally, we will examine some of the numbers to get a better understanding of the magnitude of overlap between the two disorders. Finally, we will examine some of the "warning sign" behaviors which youngsters might display before the onset of alcoholism occurs.

However, in the next entry, we will examine whether there is a hereditary factor in place surrounding brain volume, as well the prevalence of expressed outward symptoms of ADHD, and how these are both associated with an increased risk in developing alcoholism later in life.

The ADHD and Bulimia Connection

ADHD is a disorder that has numerous comorbids ("comorbids" refer to disorders that often accompany or are seen alongside of ADHD). These include, but are not limited to: Depression, Tourette's, Conduct Disorders, Sleep Disturbances, Restless Legs Syndrome, Body mass and obesity issues, dysgraphia (poor writing skills and abilities), processing disorders, sensory integration disorders as well as several others.

In the midst of all of these co-occurring disorders, there are a few that often evade the attention of both researchers and the general public. One of these is the disorder bulimia nervosa. Bulimia nervosa (which is often simply referred to as bulimia), which is often characterized by eating (and often binging) followed by purging, is a major issue in many industrialized nations, especially among teens and young women. Based on a study by Surman and co-workers, it appears that there is a relatively high correlation and prevalence of bulima and ADHD. A link to a quick synopsis of the study can be found here, but for sake of time, I will summarize a few key findings from the article:

• Impulsive behavior is a hallmark characteristic of ADHD, and impulsivity is also thought to be a major factor in bulimia as well. It is even hypothesized that some type of underlying factor may be responsible for governing both disorders.

• Given the fact that the disorder of bulimia is expressed at much higher frequencies in young females in late adolescence and early adulthood, it is interesting to note that correlations between the two disorders were relatively weak for men and non-adult women. Additionally, this is worth mentioning because the percentage of individuals with ADHD is heavily skewed towards the male side. That being said, the fact that there was not more of a correlation between ADHD and bulimia in males could be a reflection of either a poor sample size or representation of t he general population, or a relatively weak connection between the two disorders (i.e., one this is unable to override the so-called gender bias of bulimia favoring women and ADHD favoring men).

• These results were tallied from 4 relatively large sample pools previously constructed to evaluate the effects of ADHD over an extended, longitudinal, multi-year period of time. This suggests that some of these relatively strong bulimia/ADHD correlations did not appear simply due to random statistical chance.

• Like ADHD, bulimia has been tied to functional imbalances involving several systems of neurotransmitters, which include serotonin and norepinephrine. It is also possible that hormonal surges during puberty may increase imbalances of neurotransmitters like serotonin, especially in females. Since serotonin levels are tied to feelings of satiation or fullness, imbalanced in this key neurotransmitter can interfere with the feedback of normal eating patterns. In addition to social and environmental pressures, this neurotransmitter imbalance may be another contributing factor to the prevalence of bulimia, anorexia and other eating disorders in females of this age.

• Stimulant medications, such as methylphenidate, which are often the first line of treatment for individuals with ADHD, especially those showing pronounced signs of impulsivity and hyperactivity, have shown potential in the treatment of bulimia, albeit through studies with very small sample sizes.

Taking this one step further, it appears that genetics may be an additional overlapping factor involved in stimulant medication treatment for ADHD. For example, some research suggests that different forms of DAT1 may be responsible for the effects of methylphenidate on appetite and eating behaviors including purging (DAT is short for "Dopamine Transporter Gene"). We have seen previously that there is a connection between the DAT gene and ADHD. Located on human chromosome #5, DAT1 has been linked to Parkinson's, Tourette's and substance abuse.

Additionally, proteins coded for by the DAT gene are expressed in high concentrations in the basal ganglia region of the brain. The basal ganglia is essentially responsible, among other things, for determining how fast a person's brain "idles" For example, "type A" individuals, who are often workaholics, easily stressed, and always on the go at 100 miles per hour often have overactive basal ganglia, while the more relaxed, easy-going, "type B" personalities typically have less activity in this critical brain region. While there also appears to be a significant overlap between bulimia and depression, individuals with bulimia typically display higher basal ganglia activities than those with isolated depressive symptoms.

Given the prevalent distribution of this gene's expressed proteins in key brain regions like the basal ganglia, and the role of involvement of these brain regions in eating disorders, the DAT gene may be an important determining and regulating factor for bulimia and other eating disorders, especially in the context of comorbid ADHD.

Please note: These final remarks are simply this blogger's opinion on the subject:
I personally find this connection between ADHD and bulimia to be interesting. However, I do believe that we should be cautious when investigating ADHD comorbid disorders. It is tempting sometimes to fall into the trap of falsely assuming that correlation always implies causation, and trying to find underlying causes for disorders and attempting to link ADHD to every other disorder under the sun.

However, the role of the DAT genes, which have been tied to ADHD, do offer at least some credence to at least some degree of genetic predisposition to both ADHD and bulimia. This claim is further strengthened by the degree of overlap involving medication treatments of the two disorders, namely stimulants. However, there have been several documented cases of the disappearance of bulimia symptoms following treatment with methylphenidate (Ritalin, Concerta, Daytrana, etc.) for comorbid ADHD.

As a result, we may be faced with a "chicken and egg" question: "Does bulimia increase the risk of ADHD or does ADHD increase the risk of bulimia?" (or even "Are they both side effects of an even larger underlying cause?"). Another plausible explanation is that ADHD is a culmination of secondary effects involving bulimia and other eating disorders. Constant purging will typically wreak havoc on the digestive system and lead to improper food and nutrient absorption. I have hinted in previous posts that digestive disorders such as celiac disease can often manifest symptoms which closely approximate those of ADHD. Given the mounting evidence connecting ADHD (or other disorders which exhibit closely related symptoms which could potentially lead to a "false" diagnosis of ADHD if one is not careful) to nutrient deficiencies, it is quite possible that ADHD and its symptoms are secondary effects of nutritional deficits caused by eating disorders such as bulimia.

Gene Variations Which Affect Attention Control

A couple weeks ago, I posted some information on a specific gene thought to be connected with ADHD called COMT (short for Catechol-O-Methyltransferase). This gene is located on the 22nd human chromosome, and can exist in different forms. What is important to note is that the amount of stimulant medication necessary for effective dosing for ADHD and related disorders is often dependent on which forms of this gene an individual possesses. To view this (somewhat lengthy) post on COMT, please click here.

In this previous post, I mentioned that the COMT gene codes for an enzyme which goes by the same name. This COMT enzyme has two forms of interest with regards to our discussion, the "Met" form and the "Val" form. "Met" and "Val" are short for Methionine and Valine, respectively, which are two different amino acids seen at the 158th spot on the COMT enzyme.

The reason that this is so important and relevant to the topic of ADHD is that this relatively small difference in enzyme composition can have a huge effect on how much of a stimulant medication is required to reach peak chemical efficiency in a region of the brain called the prefrontal cortex.

The prefrontal cortex is located in the brain behind the forehead, and is heavily associated with the disorder of ADHD. What a recent study found was that individuals with the "Met" form of the enzyme often require significantly less "assistance" from stimulant medications to reach peak efficiency in this critical brain region during cognitive tasks, than do individuals with the "Val" form of the enzyme. To illustrate this, please refer to the diagram below, which was seen in this previous post.:




Now it appears that, in addition to the prefrontal cortex region of the brain, these two variations in this COMT gene are responsible for what goes on in other brain regions as well. This region is called the cingulate cortex. The region of this brain section which we are most interested in for this discussion is about 2/3 of the way back, closer to the center of the brain. This region of interest is around area 31 on this brain map below, which is referred to as the dorsal cingulate. Here, the word "dorsal" means "back", and the word "cortex" refers to the outer layer. As a reference, the prefrontal cortex area of the previous discussion of interest is around region 9 of the brain map below:
There are a couple of differences worth mentioning between these two brain regions. The prefrontal cortex region mentioned in the previous post is responsible for functions such as working memory (which is explained in more detail here), as well as screening out unimportant information and inhibiting inappropriate responses. We can see how this is relevant to ADHD, as improper function on this region can lead to excessive distraction by unimportant stimuli and poor impulse control. To use the analogy of a car, we might think of this brain region as a type of "braking system" for the brain.

If the prefrontal cortex region acts as the brakes, the cingulate region of the brain can be thought of as a type of "gear shifter". In addition to being relevant to ADHD, this cingulate region of the brain can also be a major factor in disorders such as OCD (Obsessive Compulsive Disorder). In the case of OCD, the cingulate region is overactive. As an analogy, think of pushing on a gear shift with too much force that the vehicle gets "stuck" in a specific gear. In the same sense, individuals with OCD often get "stuck" on a certain fixation whether it be washing one's hands repeatedly, counting cracks on a sidewalk, or repeatedly checking to make sure the oven is off.

As an interesting aside, there has been some interesting discussions on the role of the cingulate region of the brain with regards to governing events involving motor control such as hand movements. This may be one of the reasons why individuals with ADHD often have poor handwriting and difficulty taking notes.


There are some differences in chemical function between these two brain regions (the cingulate and the prefrontal cortex) as well. For the prefrontal cortex region, there are relatively few receptors and transporters for the brain chemical dopamine. Dopamine is a key ingredient for proper signaling between neurons, and a specific balance of this chemical inside and outside of nerve cells is critical for proper function. For individuals with ADHD, there is often a shortage of dopamine in the areas in between nerve cells, so this inside-outside balance is off. Many stimulant medications work to "correct" this imbalance by blocking the transport of dopamine from the outside of cells to the inside of cells in specific regions of the brain. In contrast to the prefontal cortex region of the brain, where there are relatively few of these dopamine transporting and receiving agents, the cingulate region of the brain has a much higher concentration of these dopamine-regulating areas.

The reason that the COMT enzyme is so relevant to all of this, is that this enzyme is capable of metabolizing and breaking down the chemical dopamine. We have previously seen that the "Val" form of this enzyme is more effective at metabolizing dopamine than the "Met" form. As a result, individuals who exclusively have the "Val" form, are often more prone to a shortage of free dopamine than individuals with the "Met" version.

What does this all mean?

Several studies have indicated that the cingulate region is very important in monitoring conflict and regulating behavioral control as well as governing challenging decision making processes. With regards to our discussion here, if an individual is taking an online exam and a cricket is chirping outside, the cingulate region is in part responsible for which "stimulus" is more worthy of attention. Therefore, this cingulate region of the brain plays an important role with regards to attentional control.


A brief recap of the study on COMT gene variations on the cingulate brain region:

A comprehensive study was done by Blasi and coworkers to investigate the differences between the "Met" and "Val" forms of the COMT gene with regards to attentional control. They found that individuals who had both copies of the "Val" form of the COMT gene (remember that humans typically possess two copies of a gene, one coming from each parent) had much more difficulty maintaining attention than did individuals who had both copies of the "Met" form of the gene. Individuals who had one "Val" form and one "Met" form fell in between.


Blasi's group found that in order to maintain attention for a prolonged period of time (i.e. screening out distracting stimuli that interfere with the desired task at hand), the "Val" individuals had much more activity going on in this cingulate region of the brain. In other words, this cingulate brain region had to work harder (i.e. was less efficient) for the individuals who had both copies of the "Val" form of the COMT gene, than for those who had one copy of each. Individuals who were fortunate to have both copies of the COMT gene be of the "Met" form showed the most efficient (i.e. less work needed) cingulate region of the brain, and were more effective at maintaining attention to the desired task at hand.


What is interesting to note is that this group tested the subjects on different tasks which required varying degrees of attentional control. This was done by asking the individuals to analyze the relative orientation of different sized arrows on a computer screen (see here for the the diagrams used in the study). Notice that there are three different sizes of arrows, in which seven small arrows make up a medium sized arrow and six medium sized arrows comprise a large arrow. Subjects were asked to answer which direction a given-sized arrow (either "small", "medium" or "large") was facing. Note that for the "easy" attention tasks, all 3 sizes of arrows were pointing in the same direction, while in the "medium" and "hard" attention-based tasks, the different-sized arrows were pointing in different directions.


Results of the attention-based study: The study found that the genetic effects were much more pronounced for the difficult attention control tasks than for the easier tasks. In other words, individuals with the "Met" forms of the COMT gene had a much less difficult time with this task than did individuals with the "Val" forms of the COMT gene (that is the cingulate region of the "Met" individuals required less brain activity to complete the task than the cingulate region of the "Val" individuals).

This is analogous to the results from a brain activity study involving the differences in the "Val" and "Met" gene forms on a working memory task, which utilized the prefrontal cortex region of the brain (you can find the blog post on this study here). Based on this prefrontal cortex study, the more difficult the working memory task, the more pronounced the difference between the "Met" and "Val" individuals (like in the cingulate study, the "Val" individuals' brains had to work harder). Brain activity in both studies was determined by measuring changes in blood flow to these brain regions required to complete the task, using an oxygen-detecting system (larger increases in blood and oxygen flow to a specific brain region signify harder work by that portion of the brain).


Key differences between the two brain regions regarding Val and Met differences:

While the two studies of the two different brain regions and their respective tasks (the prefrontal cortex and working memory tasks vs. the cingulate region and attention control tasks) shared a high degree of overlap in their results, there were some key differences:

• While individuals with the "Val" form of the COMT gene required greater effort in their prefrontal cortex region of their brains (as detected by blood oxygen sensors) than those with the "Met form", this overall increase in effort did not correspond to worse performances in the tests by the "Val" individuals. In other words, for tasks involving working memory, it appears that while "Val" individuals have to work harder, they can still perform at comparable levels of accuracy to "Met" individuals. However, "Val" individuals may have a more difficult time when it comes to the cingulate region, as there was a connection between an increase in required brain activity and actual performance on these tasks. In other words, "Val" individuals could be out of luck when it comes to matching performances with their "Met" counterparts when it comes to functioning during very difficult attention-maintaining tasks. Of course this is not to say that practice, training and medication treatment cannot overcome at least some of this inherent genetic disadvantage.



• When it comes to task performance requiring attention and working memory, it appears that differences in dopamine-governed signaling processes (such as those arising from "Val" or "Met" forms of the COMT gene), it appears that accuracy differences in performing tasks is more pronounced in cingulate regions of the brain, where differences in speed, reaction time and even premature decision-making are more evident in the prefrontal cortex region of the brain.
  
  
• Within the context of this post, it suggests that "Val" individuals are more prone to slower processing, poor reaction timing and impulse control on tasks involving the prefrontal cortex (such as tapping into working memory in tasks such as recalling and utilizing stored information such as math formulas or physics equations), and more likely to be error-prone with regards to tasks involving the cingulate region (such as discriminating between multiple conflicting stimuli and maintaining attention to the "correct" one).
  
  
• Taking the above one step further, this possibly suggests that if an untreated ADHD individual who has the "Val" version of both genes was taking a physics test, he or she could likely perform in a comparable manner to that of a similar individual with the "Met" form, if he or she had extra test time. This is because this type of test would likely involve working memory (i.e. recalling and then using an appropriate formula for a particular physics problem). However, if a continuous external distraction was present (such as a loud air conditioner or a flickering light or an attractive member of the opposite sex seated nearby), having extra test time would be less likely to even the playing field for our poor "Val" individual. This of course, may be stretching and over-simplifying quite a bit (of course we know that there are way more factors involved than just this), but these somewhat subtle genetic differences could possibly have some implications when it comes to discerning and providing accommodations for individuals with learning disabilities, especially in an academic or work environment.
  

These findings have medication implications as well. Based on the Prefrontal Cortex / Working Memory studies with regards to the "Val" and "Met" forms of the COMT gene, we have seen that differences in ADHD medication dosage are affected, with "Val's" typically requiring more stimulant medications than "Met's" to achieve optimal dopamine balance. However, in the cingulate brain region, another key signaling chemical called serotonin also comes into play. As mentioned previously, the cingulate region is thought to play a role in OCD, and medications of the antidepressant variety (which often boost serotonin levels and can actually indirectly reduce dopamine production, as serotonin and dopamine can sometimes act in a "push-pull" manner, where an increase in one can decrease the other) are often utilized as a medication treatment option.

This is why medication treatment strategies, can get hairy with regards to this cingulate region. On one hand, we want to tune down the dopamine-destroying effects of the "Val" form of the COMT gene in an attempt to regulate attentional control, while at the same time keep this cingulate region in check so a chemical imbalance of serotonin doesn't force this region into overdrive and result in or exacerbate OCD behavior. That is why some of these studies tying down the effects of variations of specific genes to specific brain regions can be such useful tools in determining medication levels.

I am personally convinced that in the future, individual genetic screens will become more commonplace and will play much more of a role in governing the selection and dosage of specific ADHD medications. As we begin to pin down more and more gene forms to specific regions of the brain, we will certainly be armed with more tools to fine-tune individual treatments for ADHD and related disorders and eliminate some of the guess-work in selecting medications and other treatment options.

Genes and ADHD Brainwave Patterns

There is mounting evidence surrounding the genetic basis for ADHD. Some studies place the blame on genes, as heritability of ADHD may be as high as 75 percent. Some of the specific ADHD genes under investigation can be seen here.

EEG has been a hot topic of discussion as of late for individuals suffering from attentional difficulties. Short for electroencephalography, EEG is an electrical measuring device used to monitor brainwave patterns and frequencies. In general, the higher the frequencies, the more "alert" the individual is:

Some common states and their EEG ranges can be found below. Note that the numbers are in hertz or cycles/second

Delta: 1-4, sleep
Theta: 5-7, daydreaming
Alpha: 8-12, relaxation (watching TV)
SMR (Sensorimotor Rhythm): 12-15, Focused relaxation, live sporting events, easy video games
Beta: 13-24- concentration
High Beta: over 25-30, anxiety and related symptoms

Individuals with ADD or ADHD often (not surprisingly) have more difficulty staying in the Beta range and are seen excessively in the Theta state. EEG programs are available in which the individual attempts to remain in a beta state for as long as possible. Essentially, they "train" the brain to hold a higher frequency, often through some type of interactive computer game which stops when beta frequencies are no longer maintained.

To be perfectly honest, I know relatively little about the intricacies of this procedure. However, based on what I've gathered so far on the subject, this practice seems to have had a moderate amount of success. Some consider it to be too costly or over-prescribed, while others swear by the results. Based on what I've read, typical treatment is often comprised of weekly interactive EEG treatments for a period of 1-2 years. At this point, I am not in a position to give advice on this alternative treatment measure for ADHD and related disorders, but I do find at least the theory behind it to be highly plausible.

Returning to the genetic basis surrounding EEG measurements for a moment, we see that the degree of heritability is thought to be highest somewhere around the high alpha and low beta states (right around the Sensorimotor Rhythm region mentioned above) and begins to decrease at both higher (high Beta) and lower (Delta and Theta) states. Given the difficulties of achieving a consistent Beta state for ADHD'ers, we can see that these difficulties may fall right in the eye of this storm of heritability and genetic predisposition.

A comparative study was done examining EEG patterns of un-medicated children with ADHD who had siblings or parents with the disorder. This study measured baseline brainwave frequencies and brainwave patterns when the subjects underwent a Continuous Performance Task.

In a nutshell, Continuous Performance Task tests measure both inattention and impulsivity, both of which are landmark ADHD characteristics.

How the Continuous Performance Task test typically works:
An individual may be asked to press a computer button only after seeing a specific letter or shape. If that letter or shape is shown only rarely, then the individual enters a "bored" state (which is often connected to Theta activity, which is typically higher in ADHD individuals to begin with). As a result, he or she may space out and miss when the letter or shape is finally presented on the screen. This "miss" is called an error of omission, and is reflective of inattention.

On the flip side, if the letter or shape is constantly being shown, the individual may attempt to "guess" when it is next displayed and push the response button prematurely. This is an error of commission, and is more connected to impulsivity.

Correlations in EEG patterns between siblings was much higher for measures taken in a state of cognitive activation (i.e. when undergoing the continuous performance task listed above) than EEG baseline patterns. This suggests that ADHD genetic differences are much more pronounced during cognitively challenging situations, than during rest. In other words, similarities in brainwave patterns of ADHD siblings are greater during cognitive tasks than while at rest.

• The only statistically significant EEG pattern seen between siblings at the resting or baseline state was that of the theta state in the frontal region of the brain. This is interesting to note, because this region, which includes a brain domain called the prefrontal cortex, which is thought to be one of the major "hot spots" for chemical imbalances in an ADHD brain.

• During these performance tasks, which involve periods of concentration, it was noted that correlations between sibling brain wave patterns were extremely high; higher than a cause which was purely genetic would indicate (since non-identical twin siblings only share half of the same genetic material). This suggests that among these siblings, both genetics and overlapping environmental factors are both at work.

• While all brain wave states during concentration tasks were thought to be genetically connected, it appears that changes in the alpha state (and somewhat with the theta state)were the most pronounced. This was believed to be due to an overall decrease in these overall frequency states during concentration tasks, which suggests that in order to maintain concentration for a cognitive tasks, the brains of these individuals were forced to work "harder" by operating at a higher frequency (Beta) state. To overstate the obvious, this supports the idea that ADHD brains must work harder to maintain an attention span by bumping up to a higher state.

• One note of particular interest: It appears that genetics (i.e. having at least one parent with the disorder) plays a much greater role in errors of omission (see description near the top of this post) than in errors of commission. Since errors of omission are more associated with inattentive behavior and errors of commission are more associated with impulsive behavior, it suggests that genes are more likely involved in individuals who are more of the predominantly inattentive ADHD subtype than they are for the hyperactive-impulsive ADHD subytpe.

• While genetics appeared to be connected to overlaps in brain wave states and how hard the brains of ADHD siblings had to work to maintain attention, there was little statistical evidence linking actual cognitive task performance to family-based genetic heritability. In other words, while the brains of these children with ADHD had to work harder to complete the cognitive task, the overall abilities to actually perform the task were not thought to be tied to familial inheritance (such as from the parents).

• This above point suggests two things: 1.) Individuals with ADHD are able to over-ride genetic predispositions and maintain an attention span, albeit at a higher cost, and 2.) EEG is a powerful diagnostic tool that is a more accurate predictor of genetic heritability of ADHD than are physically detectable symptoms (such as observed bouts of inattention, hyperactivity or distractibility).

While these findings are encouraging, it is important to note that EEG-based treatment of ADHD is still in a period of relative infancy. However, like the experience of watching a duck on the water (who appears to be calmly floating along while his legs are thrashing below the water's surface) EEG offers the unique ability to detect the "thrashing below the surface" of an ADHD brain. The studies above strongly suggest that there may be a much greater genetic component to this thrashing than we previously expected.