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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to hold a higher frequency, often through some type of interactive computer game which stops when beta frequencies are no longer maintained.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 Ive 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 Ive 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 ADHDers, 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 waters 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.

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Gender Age and Subtype Effects on ADHD Comorbid Disorders

We have spoken extensively on some of the related or comorbid disorders associated with ADHD ("Comorbid" here refers to an accompanying disorder that frequently occurs alongside ADHD. These may include disorders such as depression, Tourettes Syndrome, allergies, substance abuse problems and the like). The topic of this post is to investigate whether there is a pronounced gender effect on these comorbid disorders; in other words, whether boys and girls are more prone to a particular disorder comorbid to ADHD based on their gender. As we will see later, age and ADHD subtype effects are also important factors with regards to comorbid disorders.

Much of this info was taken from an article titled Gender Differences in ADHD Subtype Comorbidity by Levy and coworkers. Here is a summary of some of the main points in the study:

• Approximately half to over three quarters of ADHD children carry some type of comorbid behavior disorder. These include oppositional defiant and conduct disorders, learning disabilities and communication disorders (including speech and reading difficulties). Additionally, many exhibit anxiety disorders such as generalized anxiety disorders or separation anxiety disorders.

• Additionally, ADHD has traditionally been separated into three different forms or subtypes: inattentive, hyperactive/impulsive, or combined (a combination of the other two subtypes). All three subtypes are heavily skewed towards the boys, which outnumber girls from anywhere around 2:1 to 5:1 (some studies skew this gender difference even higher, up around 10:1). Based on the study by Levy and coworkers, here is an approximate distribution (numbers indicate overall percentages among the study population, which includes non-ADHD individuals) among the prevalence of the three subtypes for both genders:
  

As we can see, all three subtypes are skewed heavily in favor of the boys.

• Of the three subtypes listed above, it appears that the subtype (again, perhaps not surprisingly) most associated with comorbid disorders (listed in the first point) is the combined subtype.
  

• There appears to be a discrepancy between the genders as far as internal/external symptoms of ADHD and related disorders. Some studies have suggested a general trend in which many of the symptoms or problems of girls with ADHD and related disorders are more internalized (i.e., they do not outwardly manifest themselves as readily as boys), which may contribute to the skewed gender differences mentioned above. On the contrary, the same study suggests that external or outward symptoms are more apparent in boys, which may compound this effect.

• Reading disabilities are, perhaps not surprisingly, more common in children with ADHD. It appears that reading disabilities correlate more to "internal" symptoms in girls and "external" symptoms in boys with ADHD, however, reading disorders appear to have very little overlap with conduct or oppositional behaviors such as aggression or delinquent behavior. Furthermore, reading difficulties appear to be more related to the inattentive side of the disorder of ADHD than the hyperactive/impulsive side of the disorder. In other words, the inattentive and combined ADHD subtypes are significantly more likely to have problems with reading than the exclusive hyperactive/impulsive subtype for both genders. It appears that reading difficulties and inattentive behavior may have an even stronger correlation in girls.

• Furthermore, with regards to reading and speech disabilities, there is a strong gender difference for non-ADHD individuals. However, once the disorder of ADHD is introduced, the gender difference becomes less of a factor (this holds for all three ADHD subtypes). This may at least suggest, that ADHD symptoms may override or overpower what appears to be more subtle gender differences with regards to speech and reading disorders.

• There is a significant association between generalized anxiety disorders and ADHD for both genders. Gender differences for the combined ADHD subtype were especially pronounced, with rates among females with the combined ADHD subtype being significantly higher than the combined subtype males. In addition, the combined subtype was more associated with generalized anxiety for both genders (when compared to the inattentive subtype), which suggests that hyperactivity/impulsivity may play some sort of role in generalized anxiety for both genders.
  

• With regards to separation anxiety disorders (such as from parents or loved ones), it also appears that there is a higher correlation to girls with ADHD, especially with regards to the inattentive ADHD subtype. For boys, the separation anxiety disorders were highest for the combined ADHD subtype. The study suggested that separation anxiety disorders may be a sign of immaturity for both genders, and may be indicative of later "internalizing" problems in girls. Furthermore, this assertion is in agreement with several studies which associate ADHD with a delay in maturity.
  

• Based on the two findings above, in which girls with the inattentive ADHD subtype had higher rates of separation anxiety disorders and girls with the combined subtype having increased rates of generalized anxiety disorders (both of which are considered more "internal" symptoms) than their male peers, it may be suggest that screening for ADHD in girls who exhibit anxiety disorders may be beneficial, in that it may reveal underlying comorbid ADHD and offset some of the skew among gender differences and ADHD.

• Finally, age has been shown to be an important factor with regards to symptoms and severity of ADHD comorbid disorders. In this study, comparisons were done between the younger (ages and and under) and older (ages 11 and older) children in the study population. For males, the prevalence of most of the comorbid disorders (speech and reading difficulties, oppositional defiance, generalized and separation anxieties) decreased with age, with the notable exception being conduct disorders, which increased with age. For females, age was less of a factor for all of the comorbid disorders listed above with the exception of Separation Anxiety Disorders, which decreased with age (supporting the earlier assertion that this disorder is tied to maturity levels and would naturally decrease as a child gets older). In addition, inattentive symptoms associated with ADHD actually increased with age for the female population of the study. This was the exception to the overall trend of decreasing ADHD symptoms with age, which was seen in the other two subtypes for females and all three subtypes for males.
  

I would like to conclude with a final note of personal opinion. I firmly believe that when screening, diagnosing and attempting to treat ADHD and comorbid disorders, we employ far too little emphasis on the gender differences surrounding these disorders. This can lead to several potential problems such as stereotyping or pigeon-holing certain behaviors (i.e. attributing hyperactivity/impulsivity as being a "male" characteristic and either intentionally or unintentionally overlooking these symptoms or behaviors in girls).

In addition, it appears that girls may have a higher prevalence of the more "internal" comorbid disorders such as anxiety, which are often more difficult to detect than the more outward comorbid disorders of oppositional defiance and conduct disorders. This may play a major part in the gender discrepancy of ADHD diagnosis, which may leave a number of girls with ADHD undiagnosed and untreated.

Additionally, the more "internalized" nature of female cases may also lead to a lack of diagnosis and treatment for comorbid disorders associated with ADHD as well. The Levy study pointed this out, citing the discrepancy between referrals for ADHD-related reading disabilities. Reading disorders for boys were more likely to be associated with some of these outward characteristics, while girls with reading disorders exhibited more of the aforementioned "inward" traits. As a result, the rates of referral for boys with reading disabilities (based on their overall representation in the population) was almost twice that of girls.

Furthermore, this study by Levy, as well as several others, indicate that there are several (sometimes unusual or counter intuitive) associations between gender, and ADHD subtype and the expression of symptoms of specific comorbid disorders. For example, attributing an increase in Separation Anxiety disorders to younger females with the Inattentive ADHD subtype or Conduct Disorders to the Combined ADHD subtype in males may give us some possible insight as to which subpopulations of ADHD children are most "at risk" for developing some of the aforementioned comorbid disorders.

Since several of these comorbid disorders carry their own lines of medication and other treatments, the subclassification of ADHD children based on age, gender and subtype may be especially beneficial with regards to developing successful individualized treatment plans. I firmly believe that by separating out and subcategorizing ADHD and its comorbid disorders based on factors such as age, gender and subtype whenever possible could lead to a new a wealth of information for diagnosing and treating ADHD and its associated comorbid disorders.

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Food Allergies Change Brain Electrical Activity and Results in ADHD Symptoms

The connection between food allergies and ADHD has been a hot topic of debate in recent years. A number of studies have shown that adverse reactions to specific foods or combinations of foods and food additives can exacerbate several of the trademark characteristics of ADHD, including hyperactive behavior and reduced attentional ability. The aim of this post is share how adverse reactions to foods can actually impact brain wave frequencies in specific regions of the brain, which in turn leads to an increase in ADHD symptoms.

Returning to our topic of discussion, there has been relatively little research done on the actual mechanisms of the effect of food allergies on ADHD symptoms. However, there was a 1997 study done by Uhlig and coworkers which is of potential interest. This group studied the effects of food allergies on changes in brainwave frequencies throughout sixteen different regions of the brain. Note that we have discussed the topic of brainwave pattern differences in individuals with ADHD in an earlier post titled Genes and ADHD Brainwave Patterns. A summary of the components key findings of the study are listed below:

• Twelve children with known food allergies (not severe enough to pose a danger) had their brain wave patterns measured via EEG (electroencephalography) in sixteen different brain regions after both a 5 day period of consuming the allergy-provoking foods and a two-week period of avoiding these foods, and the results were compared between the two measurements.

• 10 of the 12 children had previously been tested and shown to have Conners rating scale scores that were below the threshold for ADHD when the provoking foods were avoided and above the threshold when the foods were included in the diet. In other words, with all other things being equal, consumption allergy-provoking foods caused enough of a change in symptoms to push all twelve of the individuals over the threshold and into ADHD territory. A quick summary of the huge difference in most of the scores can be seen in the table below (note that the "cutoff" score for ADHD is 15 or above for the scale being used, these numbers are highlighted in black):

Note that significant changes in the Conners rating scale were seen in all 12 children, and 10 of the 12 childrens scores crossed the ADHD threshold score of 15 with regular consumption of provoking foods, including one who made a huge jump from 6 all the way up to 25. This shows how intolerance to specific foods can have a huge impact on Conners rating scale scores and can easily push a child over the limit and can lead to an ADHD diagnosis. If these foods (with which the individual is often unaware of being provoking and a cause of an increase in ADHD symptoms) are consumed on a consistent basis, it is easy to see how 6 continuous months of symptoms can occur and lead to an ADHD diagnosis. While this is based on a small sample, and was not the main purpose of the study, these findings really do raise questions as to how many cases of ADHD arise simply from food-related intolerances, and can be changed by removal of the provoking foodstuffs from the diet (we will be investigating more on this topic in later blog posts).

• The most common foods provoking ADHD symptoms in the study were beet sugar, food colorings, wheat and milk.

• Frequencies corresponding to eight different brain wave states were obtained in 16 different regions of the brain. A summary of the numerical frequencies of these eight different states (in Hertz, or cycles per second) and their corresponding brain wave types and approximate brain activity levels are listed below:

• Out of all of the frequencies listed above, the beta-1 brainwave frequency was believed to be impacted the most by food allergies. Interestingly, it appears that the beta-1 brainwave frequency changes appeared to be concentrated the most in the right frontal and temporal regions of the brain (keep in mind that the different parts of the brain do not operate at uniform frequencies, for example, some regions may be in a predominantly beta-1 state while others are operating at a theta state). This area is also one of the brain regions most associated with ADHD, as we have seen in earlier posts. An outline of the areas with the greatest change in beta-1 activity is given in the diagram below:
  

The approximate locations of the 16 different brain regions probed for beta-1 brainwave frequency changes in the Uhlig study are given above (as one would see from a top-down view of the head). The larger blue squares indicate brain regions of greatest change in beta-1 activity between the two EEG scans (one after prolonged consumption and the other after prolonged avoidance of allergy-provoking foods). The smaller blue squares indicate regions of smaller (but still statistically significant) changes between the two EEG measurements. The white squares indicate brain regions that saw minimal change in beta-1 activity.

We should also note that the brain regions most affected by food sensitivities also happen to be the same areas most connected to ADHD, as we have seen in previous posts, such as the one on differences in brain region blood flow patterns in ADHD.

• While the Uhlig study showed significant changes in beta-1 activity due to food-sensitivity effects, alpha activity changes were minimal. Other studies have indicated that diseases with reduced blood flow to the brain (which can include ADHD) are more associated with changes in delta and theta brainwave activities. As mentioned in the brainwave chart in this post, theta activity, which is essentially a daydreaming state, is (not surprisingly) seen more consistently in individuals with ADHD than in the general population. On another interesting note, adults with anxiety-type depression have also been shown to exhibit an increase in beta-1 activity in similar brain regions.
  

In this bloggers opinion: The above point suggests that there may be at least two different major causes of ADHD, which are associated with different brainwave states. The "food-sensitivity ADHD", which is associated with beta-1 frequency changes suggests an entirely different mechanism of cause and action than does the "reduced bloodflow ADHD", which is characterized by theta and delta brainwave frequency changes. This, of course, is simply a hypothesis, but looking down the road with regards to diagnostic and treatment measures, we could be using EEG to diagnose whether the underlying cause as to whether someones ADHD is either the food-sensitivity derived beta state or the reduced bloodflow-derived theta or delta state. In other words, by examining to see whether the beta-1 activity in the front part of the brain or the theta or delta activity is more disrupted, we could possibly use brainwave frequency changes distinguish between multiple underlying causes of ADHD. Of course, this presupposes that brainwave frequency differences are contributing causes of (as opposed to indicators of) ADHD.

There are two key points we should take away from this article:

1. Consumption of foods of which one may have an allergy or sensitivity to can have a huge effect on ADHD symptoms, as we saw from the Conners rating scale score differences in this post. The fact that most children fell below the threshold score for ADHD when they avoided the provoking foods, but above it when they consistently consumed them should raise an alarm. While the ADHD/food allergy connection has been around for years, the sheer magnitude of the difference in scores (albeit from a smaller sample, which often will produce greater fluctuations in score differences because extreme individual cases stand out more). Of course not all ADHD cases are due to food allergies, but this study should lend credence to the potential effectiveness of eliminating specific foodstuffs (remember that beet sugar was the most common food sensitivity in the study) in treating at least some of the cases. Furthermore, monitoring for changes in beta-1 brainwaves, especially in the brain areas mentioned above via EEG may be an extremely effective tool of the future for diagnosing (and eventually treating) food-related ADHD symptoms.
   
2. The pronounced changes in beta-1 activities highlight the surprisingly strong connection between the digestive system and the nervous system, as changes in conditions in the gut can result in extensive changes in neurological symptoms. We will discuss this connection in greater detail, as well as its implications on ADHD at a later time.
   

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Genes and Low Birth Weight Combine to Increase Risk of Conduct Problems Alongside ADHD

In the past, we have investigated the role of the COMT gene and its effects on the onset and severity of ADHD cases. Now it appears that this gene may play a role not only in the ADHD itself, but conduct or behavior disorders which often occur alongside (or are comorbid to) of ADHD.

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Food Additive Combinations and ADHD

The concept of food additives, which include artificial colors and flavorings used in food processing, and their influence on ADD and ADHD is nothing new. Starting in the mid-1970s by Feingold as well as others, the idea that artificial food ingredients may have some type of pharmacological impact on neurodevelopmental disorders became a hot topic of discussion.

Today, the debate rages on as to how much of an effect these chemical ingredients really have on our systems. I am not going to lend my full support to either side of this discussion any time soon, because the evidence is strong for both arguments. Instead, I wanted to look at a less-discussed but equally important topic on the effects of food additives and ADHD, namely the synergistic effects of these compounds.

In terms of our discussion today, a synergistic effect is where two or more compounds or chemicals, when used in combination together, result in a greater impact than the sum of their individual effects (the concept of the "whole" being greater than the "sum of the parts"). For example, if a specific concentration of food chemical "A" reduces nerve cell growth by 10% and a specific concentration of food chemical "B" reduces growth by 15%, then, theoretically, a combination of these two concentrations together should decrease cell growth by about 25%. However, if the two chemicals combined (and all other factors being carefully controlled) reduce growth by, say 50%, then the cause is likely a synergistic effect or interaction between chemicals "A" and "B".

The investigation into synergistic effects of food additives stems from an article done by Lau and coworkers on how four food additives, well-known for their potential neurotoxic effects as individual agents, can potentially be even more devastating when used in combination.

The four food additives in question were as follows:

1. Brilliant Blue, also referred to as "Blue1" and "E133" (in Europe)
2. Quinoline Yellow, also referred to as Yellow 13 or E104
3. Aspartame (Nutrasweet, Equal): and artificial sweetener often used in diet soft drinks
4. MSG: short for Monosodium Glutamate or a salt form of L-glutamic acid, often used in Chinese foods and, (to a lesser extent now), potato chips and french fries

The study found that two pairings of the above compounds had notably significant synergistic effects. Brilliant Blue, when combined with MSG, showed a strong decrease in a process called neurite outgrowth. Neurite outgrowth, essentially, is the process where neurons begin to develop and differentiate, and eventually results in the interaction of neurons with either other neurons or cells of different systems such as muscle cells. In addition to the Brilliant Blue and MSG combination, the combination of Quinoline Yellow and Aspartame also showed a strong additive effect on inhibiting neurite outgrowth.

The process of neurite outgrowth is a major indicator of overall cell health with regards to the nervous system. Additionally, this process is especially critical during the neurodevelopmental stages, which starts during embryonic development, and can continue on until an individual is in his or her 20s. However, the period of greatest development (and greatest potential sensitivity to chemical agents), is between the sixth month of gestation to the first few years after birth. As a result, (in my humble opinion) anything that inhibits this process, should be taken seriously, especially during the early developmental stages in life.

It is also worth mentioning that the levels of these different chemical agents done in the study by Lau were below concentrations which typically cause neurotoxic problems on their own. In other words, these two combinations (Quinoline Yellow/Aspartame, as well as MSG/Brilliant Blue) showed extremely pronounced effects with regards to inhibiting key neurodevelopmental processes. Between these two combinations, the combined effects of Quinoline Yellow and Aspartame were more pronounced than the MSG/Brilliant Blue.

As far as the status of these four agents is concerned, three of the four (MSG, Brilliant Blue and Aspartame) are currently available in the United States, with Quinoline Yellow being banned. In the United Kingdom, where the study was done, all four of the compounds were still used in food processing. Brilliant Blue, while used in the US and UK, has been banned in most of Europe.

It is believed that the two flavor enhancers, aspartame and MSG both work via a type of biological receptor proteins called NMDA receptors. Without going into too much detail here (we will save the NMDA receptor topic for future posts), NMDA receptors play a huge role in the regulation of ion channels, which are critically important in a number of processes in a number of systems, including the nervous system. One of the key "target molecules" for these NMDA receptors is glutamate, which, as weve seen above is the major component of MSG. Additionally, part of the molecule of Aspartame is comprised of a form of aspartate, which is a form of a common natural dietary amino acid and is chemically similar to glutamate.

The reason that the above information is relevant to our topic of discussion is that glutamate and NMDA are both key biological agents involved in neuro-signaling processes which are significant factors with regards to ADHD and other disorders. In other words, chemical agents which interfere with this NMDA/glutamate "channel", often can, at least in theory, have an effect on the onset and symptomology of ADHD. We will go into much more detail on this process in later blog entries.

In addition to these concerns, we must also be aware of the fact that the NMDA receptor is a target of a number of different drugs and pharmacological agents. As a result, there is also the potential for synergistic effects between food additives and NMDA receptor drugs. In addition to current concerns of negative drug-drug (and now food additive-food additive) interactions, we must also be careful with regards to potential drug-food additive interactions. These interactions are easy to overlook, and, given the abundance of artificial food additives, are almost impossible to avoid completely.

Even if these four agents listed above all become banned at some point, I personally believe that this study should raise an alarm and open the way to a number of future studies on the effects of specific combinations of food additives. As highlighted in the article, one of the main problems with "elimination" diets for food allergies or toxicities, is that they often examine the food compounds in isolation, as opposed to combination. This study hopefully sheds some light on the fact that, perhaps, instead of just looking at individual food additives and their negative effects on ADHD and other neurodevelopmental disorders, we should be paying an equal amount of attention to investigating the negative effects of different combinations of these ingredients, especially the most common food-additive combinations that are currently available.

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Genes Omega 3s Alcohol and ADHD

The diagram above may look quite complicated, but were just focusing on a few of the objects listed above.





A number of these desaturase enzymes are all coded from a specific genetic region located on the 11th chromosome in humans, located at the 11q25 region (chromosomes have 2 "arms", a "p" and a "q", the numbering refers to relative location on that arm, so "11q25" refers to the 25th region on the "q" arm on the 11th chromosome). Interestingly, this region is located near the 11q22 region, which has been linked to ADHD. The closer two genetic regions are, the higher the chances they will be co-transmitted (passed on together from parent to child). In other words, gene forms which are located near each other on a chromosome are more likely to be passed on together, suggesting the possibility that the 11q22 ADHD region may in fact be influenced by some of the genes from nearby 11q25 region.

Brookes and coworkers did a study on the association between these desaturase genes and ADHD (on a personal note, I would like to acknowledge the authors of this particular study. Much of the information in these past two posts is gleaned from their work, and this paper provided a great starting point for much of my research for this post). They found that the 11q25 region contained three genes which code for desaturase enzymes located next to each other: Fatty Acid Desaturase 1, Fatty Acid Desaturase 2, and Fatty Acid Desaturase 3 (abbreviated as FADS1, FADS2 and FADS3, respectively). These genes each exist in different forms, called alleles, which have slightly different DNA configurations (which can differ by as little as one letter in the DNA "code").

Key findings from the Brookes study: This group saw a significant difference in the prevalence of ADHD stemming from two different alleles in the FADS2 gene. It appears that a single point difference was all it took to boost the likelihood of association with ADHD. Individuals with ADHD were significantly more likely to have the "C" form of the FADS2 gene than the "T" form of the gene at marker 498793 (this number just gives the detailed location on which spot of the DNA this form can be found).

Additionally, it appears that the onset of ADHD stemming from prenatal alcohol exposure may be somewhat genetic as well. For individuals who were exposed to alcohol via maternal consumption during pregnancy, there is some nominal evidence linking "G" allele instead of the "C" allele at two different locations on the FADS1 gene was correlated with a higher likelihood of being diagnosed with ADHD. However, the authors concluded that this connection was only "speculative".

This possible ADHD/genetics/fatty acid consumption/alcohol exposure connection is somewhat intriguing. The study established a strong ADHD connection to a specific allele of the FADS2 gene on the 11th chromosome, and also cited a number of other studies on the effects of omega-3 consumption on ADHD symptoms, but the connections with alcohol are more strained. Nevertheless, the findings from other studies offer support for this possible alcohol association with these other factors:

1. We have seen before that omega-3 fatty acid deficiencies are more prevalent in individuals with ADHD. The previous post describes the process of how omega-3s affect cell membrane integrity, which, in turn, can effect the passage of key chemical signaling agents such as dopamine (which has repeatedly been found to deficient in specific brain regions of ADHD individuals). The desaturase enzymes, which are products of the genes listed above are partly responsible for the process of omega-3 metabolism and incorporation into the cell membranes.



2. Different alleles (alternate forms of a gene) can result in slightly different forms of these enzymes, some of which are more efficient than others. In other words, enzymes coded for by one form of a gene are somewhat better at metabolizing omega-3s and incorporating them into cells than the "alternate" enzymes coded for from the "alternate" forms of the gene. As a result, small changes in the gene code in these aforementioned regions can indirectly affect the efficiency of omega-3-to-membrane incorporation.



3. Several studies have pointed to the the connection between alcohol and fatty acid metabolism in animal models of ADHD.



4. It also appears that an individual may be able to "recover" from some of the negative effects on cognition due to alcohol exposure by an increase in dietary omega-3s. This includes increasing maternal dietary levels of omega-3s during pregnancy (based on animal model studies).
   

To summarize the whole post (as well as the previous one), it appears that omega-3 fatty acid metabolism plays a major role in ADHD. This is thought to be at least in part to the effects of omega-3s on maintaining cell membrane structure and integrity and their effects on regulating levels of the brain signaling agent dopamine (which is a crucial neurotransmitter and is often deficient in ADHD cases). However, properly functioning enzymes are required for these steps. Desaturase enzymes are coded for by a genetically "hot" region for ADHD on the 11th chromosome in humans. Different versions of these genes can result in a reduction in enzyme function and potentially affect the way these omega-3s are metabolized. In mammals, alcohol exposure can also lead to reduced desaturase enzyme activity. Additionally, there is at least some evidence that alcohol can increase the likelihood of specific forms of FADS1 gene giving rise to ADHD. This may be due to the two factors combining to reduce desaturase enzyme activity to a point where omega-3 metabolism falls past a hypothetical "break-point" resulting in a sharp increase in the onset of ADHD and other related disorders.

We have been focusing heavily on the ADHD and alcoholism connection for the past couple of weeks. We will be investigating a few more studies on this connection in the upcoming posts.

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