ADHD and Vitamin D Deficiency: Any Evidence?

Is there any link between vitamin D levels and ADHD? A review of the current evidence:

We have spent a lot of time looking at correlations between vitamins, minerals, omega-3 fatty acids and amino acids (and their deficiencies) and ADHD. However, it is important to note that just because low levels of a particular nutrient are seen alongside the disorder, it does not necessarily mean that this deficiency is the cause of ADHD (i.e. correlation does not imply causation). In other words, the nutrient deficiency and ADHD symptoms might both be secondary effects of a larger primary cause, such as an enzyme deficiency or metabolic dysfunction.

In the case of vitamin D, the association with ADHD is a lot more muddled than with some of the other nutrients which have a relatively strong connection with the disorder (iron, zinc, magnesium, and omega-3 fatty acids to name a few). The amount of information in the literature is relatively scarce, as well. A search in the journal database Pubmed (where this blogger gets most of his articles and information) for "ADHD" and "vitamin D" turns up only a small handful of search results, the majority of which focus on other disorders and only mention ADHD peripherally.

However, given the fact that vitamin D is such a "hot" vitamin and has been a popular supplement as of late, we should investigate some of its potential benefits with regard to ADHD and related disorders. Please keep in mind that many of these points below are more theoretical or speculative, because most of the hard, concrete evidence in well-documented clinical controlled studies simply does not exist at the moment. Nevertheless, here are some possible ways in which vitamin D may help in cases of ADHD or related disorders:

• Vitamin D can boost levels of the antioxidant glutathione in the brain. One way that vitamin D does this is by regulating an enzyme called gamma-glutamyl transpeptidase, which plays a role in both the metabolism and recycling of glutathione. We have spoken at length about how antioxidant deficits can worsen ADHD symtpoms, and how fatty acids (namely omega-3's) are frequently administered for ADHD and related disorders. Given the high makeup of these omega-3 fatty acids in the brain, and their susceptibility to oxidation and damage in the central nervous system, protecting them by boosting antioxidant levels (either directly or indirectly) is a good bet.
  
  
• One of the current theories surrounding ADHD is that it is (at least partially) an energy deficiency syndrome, or is the result of impaired metabolic abilities in key regions of the central nervous system. While highly debatable, this theory holds that impaired glucose metabolism in various parts of the brain may be a major contributing factor to the presence or severity of this disorder.
  
  While this blogger is currently neutral on this deficiency theory, it is interesting to note that vitamin D can help regulate glucose tranport into the brain, which would (at least in theory) improve this possible cause of the disorder. It is believed that vitamin D works by targeting multiple enzymes involved in glucose transport and metabolism. Much more study needs to be done to confirm this assertion, but this may be another potential benefit of boosting vitamin D levels in the ADHD patient.
  
  
• Vitamin D may play a role in catecholamine synthesis. Catecholamines include the neurotransmitters dopamine and norepinephrine, both of which are believed to be tightly regulated and highly involved in the treatment of ADHD (deficiencies of both dopamine and norepinephrine in the "gaps" between neuronal cells are often seen in cases of ADHD).
  
  
• Vitamin D boosts the effects of an enzyme called choline acetyltransferase in the mammalian brain. This enzyme is used in the manufacture of another neurotransmitting agent called acetylcholine. Acetylcholine is thought to play a major role in maintaining a state of sustained attention, a critical shortcoming in those with ADHD. In other words, keeping adequate levels of vitamin D could potentially help prop up lower levels of this attention-sustaining neurochemical.
  
  
• Learning and memory deficits, both of which are heavily present in the ADHD population, have been tied to prenatal vitamin D deficiencies in the rat model. This involves a process called synaptic plasticity, which relates to memory formation in an individual. If this finding extends to humans, it could have serious implications on maintaining adequate vitamin D intake in pregnant women.
  
  
• Problems with fine motor control are sometimes seen as a secondary characteristic in a fraction of the ADHD population. These problems may be exacerbated in a vitamin D deficient state.
  
  
• Perhaps the strongest correlation, however, may be between vitamin D and depressive-like symptoms, particularly those associated with seasonal affective disorders (SAD). Please keep in mind, however, that studies on vitamin D levels and depression are highly variable; a number of studies have been done on the topic and found no such linkage between the two. We have previously investigated possible connections between ADHD and SAD in an earlier post.
  
  This may make intuitive sense, since vitamin D production is triggered by sunlight, so in the dark winter months, the levels of this vitamin are often much lower (this may also be a major contributing factor as to why illnesses run so much more rampant during the winter months). In other words, vitamin D supplementation may be particularly useful in individuals with ADHD who also have co-occuring depressive or anxiety-ridden symptoms.

To summarize: Vitamin D does not have as many pronounced direct effects on ADHD as do some of the other vitamins, minerals, fatty acids and amino acids we have previously discussed. Nevertheless, the vitamin does seem to have multiple neurodevelopmental and neuroregulatory properties, and may go well with comorbid disorders such as schizophrenia, speech difficulties, memory problems, and (perhaps most strongly) depressive symptoms. Please keep in mind, however, that it may not be possible to simply "supplement these problems away" with extra vitamin D. This blogger just wants to point out that a deficiency in this vitamin often manifests itself in many ways, some of which closely parallel ADHD or related disorders. Nevertheless, supplementing may not be a bad idea, especially if you live in an area that gets minimal sunlight for part of (or all of) the year. Some rough guidelines for vitamin D intake can be found here.

ADHD gene ADRA1A: A good target for clonidine?

Does the gene ADRA1A affect ADHD comorbid disorders? Is it connected to clonidine's positive response in some ADHD patients?

This blog has spent a considerable amount of focus on genes connected with ADHD. Although genetic studies surrounding the disorder are often inconclusive (and often difficult to replicate or even contradictory), the high rate of prevalence of the disorder within families and the strong genetic component of ADHD (this blogger has seen some studies reporting it as high as 90%!), any new findings for genes associated with ADHD can be noteworthy.

Furthermore, the medication treatment options for ADHD can be cumbersome as well. Some medications, such as clonidine, while not intended to treat the disorder, can often work quite well when applied as an "off-label" treatment for ADHD. The question is why?

Gene-drug interactions are an increasingly popular and meaningful component of pharmaceutical research. As we are generally moving in the direction of individualized medication strategies, and away from one-size-fits-all pharmaceutical treatment for disorders as complex and diverse as ADHD, specific genes and the target proteins which they encode, are becoming increasingly relevant in the tailoring of individual treatments for ADHD and related disorders.

The ADRA1A gene and how it relates to ADHD and other comorbid disorders:

ADRA1A is located on the 8th human chromosome, which is believed to be one of the "hot" regions for finding genes affiliated with ADHD and related disorders. The "8p" sub-region of the 8th chromosome is believed to be connected to numerous other disorders as well, including psychiatric disorders such as schizophrenia and autism.

The gene is also believed to be associated with hypertension, a disorder which is frequently targeted by the anti-hypertensive clonidine. There is some evidence that the actual mechanism of hypertension as it relates to ADRA1A may actually be due to auto-immune related causes. If this is the case, then it may warrant further exploration into other auto-immune disorders, such as allergies (which can elicit ADHD-like symptoms, and are a relatively common comorbid disorder to those diagnosed with ADHD).

The ADRA1A gene "codes for" the production of a protein known as the alpha 1A-adranergic receptor, which a target of epinephrine (adrenaline) and norepinephrine (noradrenaline). Norepinephrine is an important neuro-signaling agent which is often imbalanced in key regions of the nervous system in many ADHD cases, and is a target of several ADHD medications, including atomoxetine (Strattera) and stimulant medications such as amphetamines. The alpha 1A-adranergic receptor has also been implicated in studies of traits common to ADHD. For example, stimulation of this specific receptor has been shown to decrease impulsivity, improve working memory, and increase vigilance (in the rat model). This particular receptor is also a target of clonidine.

Given the fact that drug treatment for comorbid disorders can often alleviate some of the co-existing ADHD symptoms as well (and given the fact that ADHD is believed to be connected to circulatory impairments including reduced bloodflow to specific brain regions associated with impulse control), it is possible that those individuals possessing the "wrong" forms of the ADRA1A gene and suffer from hypertensive disorders may be prime candidates for treatment with clonidine to alleviate ADHD symptoms. In other words, specific variations of the ADRA1A gene may make one more or less likely to have a successful response to clonidine as a treatment for not only hypertension, but also co-existing attention deficit and hyperactivity disorders. Additionally, clonidine can also be used to augment the effectiveness of stimulant medication treatments for ADHD and reduce negative side effects.

Indeed, variations within three subsections of the gene ADRA1A were associated with around a 50% higher likelihood of having ADHD, according to a recent study (although when taken as part of a multi-gene analysis, the effects were not as pronounced). The rate of occurrence of each of these three variations was roughly between 25 and 50% of the study population. In other words, these are not some rare or exotic mutations we're talking about, but relatively common forms of the gene seen in the population (those of European ancestry in particular).

While not directly related to other disorders sometimes seen alongside ADHD, the genetic proximity of ADRA1A to other genes in the human genome may be noteworthy. For example, ADRA1A is located in the same subsection of the 8th chromosome (8p21) as another gene whose mutations may lead to an increased risk of epilepsy. This may be important, because in general, the closer 2 genes are to each other on a chromosme, the more likely they will be transmitted together from parent to offspring. Thus, a parent who has both the "epilepsy" mutation and the ADHD-specific ADRA1A mutation(s) may stand a greater chance of passing these gene forms on together to their child. As far as treatment is concerned, there is general consensus that clonidine is safe for patients who are diagnosed with co-existing epilepsy, however a few case studies suggest that caution regarding clonidine and epilepsy may be needed. We have investigated complications in treating ADHD and comorbid epilepsy in earlier posts.

Interestingly, the 8p21 subregion of the 8th chromosome is also home to genetic regions believed to be affiliated with schizophrenia. There is some evidence that clonidine may be an effective augmentative treatment for schizophrenia when used in conjunction with another drug haloperidol. Thus, for individuals who exhibit symptoms resembling ADHD and schizophrenia, clonidine may be a potentially useful medication strategy to try under medical supervision.

It is important to note that many of these suggestions are largely hypothetical at the moment. Do not attempt to follow any of these suggestions without medical supervision. Nevertheless, given the complexity and variability of ADHD and the compounding effects of comorbid disorders, it is useful to investigate medication strategies which have shown to be historically useful in treating multiple disorders which can often occur alongside each other. This is particularly useful for ADHD, where constraints are often necessary for medication treatments due to the negative impacts that these ADHD drugs may have on other accompanying disorders. As a result, the potential of clonidine in treating a diverse range of disorders (which may, possibly by way of ADRA1A and other nearby genes share an underlying genetic predisposition), move this traditionally second or third-line medication closer to the forefront as a valid medication-based ADHD treatment option.

Modafinil: An alternative treatment for ADHD and comorbid substance abuse?

Can Modafinil (Provigil) Replace Stimulant Medications in Adult ADHD where stimulant drug abuse is a concern?

It is a Catch-22 of the ADHD world. An individual is suffering from severe ADHD symptoms and appropriate stimulant medications may help remedy some of the negative side effects of the disorder. However, due to the high prevalence of substance abuse in ADHD (some officials put the rate of comorbid substance abuse as high as to 30% in the ADHD population), including stimulant medications such as amphetamines, treatment of ADHD symptoms via stimulant medications cannot, by nature of the comorbid substance abuse disorder, be a treatment option.

The appearance of (relatively) novel non-stimulant medication alternatives such as Strattera (atomoxetine), have offered individuals with ADHD another treatment alternative. However, the results are often mixed. Strattera often works well with the inattentive-dominated forms of the disorder, but the positive results are often not as pronounced for the more hyperactive or impulsive forms of ADHD, especially if comorbid disorders such as conduct-related issues surface.

Another alternative may be a completely different type of drug, which, while not a stimulant in its own right, can act on or exhibit pseudo-stimulant properties. It appears that in at least some cases, Modafinil (Provigil) may be the type of drug we're looking for in these cases.

**Blogger's note: The extent of the study highlighting this case for Modafinil treatment for ADHD and comorbid amphetamine abuse is intended for adult treatment only. Given the relative scarcity of research on medication options for adult ADHD symptoms (compared to those designed more for children), this post is designed for offering a possible treatment alternative for ADHD in adults. Nevertheless, some recent studies have shown promising results of Modafinil as an ADHD treatment method for children and adolescents.

It is important to note, that while not initially designed as an ADHD-specific medication (and not a stimulant in its own right), Modafinil does share at least some degree of overlap with several stimulant agents for ADHD treatment. One is its regulation of catecholamines (important neuro-signaling chemical agents, whose balance in and out of neuronal cells is crucially important for regulating attention, hyperactive and impulsive behaviors, and locomotor control). As far as its mode of action and metabolism (clinical pharmacokinetics of Modafinil) are concerned, drug-drug interactions between Modafinil and several ADHD stimulant medications such as methylphenidate or dexamphetamine (Dexedrine) appear to be limited.

A background note on addiction potentials of ADHD drugs: This section is an aside, and is meant to serve as some background information and to clear up potential confusion surrounding ADHD medications and their addiction potentials. The next four paragraphs may be skipped if you are pressed for time.

While I cannot stress enough the importance of regulating neuro-chemical balance for both the onset of ADHD as well as drug addiction (which are affected by pharmacological agents such as ADHD medications, in varying forms), it is the rate of action for which these chemical changes take place which typically drives a particular drug's addiction potential.

Unfortunately, this last fact is often lost in much of the literature surrounding ADHD treatment (especially those which promote non-pharmaceutical treatments for the disorder). For example, many "natural" ADHD treatment books and websites frequently start out by asserting (erroneously) that methylphenidate is the equivalent of crack cocaine, and promotes later drug abuse and addiction.

While this blogger is a personal advocate for natural approaches to treating ADHD whenever possible (and without compromising overall treatment effectiveness in ADHD treatment), he wants to make it clear that significant differences do exist between ADHD medications and stimulant street drugs. One of the most telling signs of this is the rate of uptake and clearance of drug-like agents into and out of the brain, respectively. In general, the quicker a substance is taken up into the central nervous system and the faster it clears the brain, the more likely this chemical agent will elicit a "high" and an increased tendency towards substance dependence.

ADHD medications like Ritalin, while having some degree of overlap in structure and net effects of action as cocaine, are specifically designed to have a much slower rate of release and clearance, significantly reducing their abuse potential compared to cocaine. We have previously discussed Ritalin (methylphenidate) vs. cocaine addiction potentials in earlier posts.


Modafinil: Modes of action and addiction potential:

The reason I am providing all of this information is the fact that the successful regulation and softening of rapid spikes and clearances of chemical peaks is a crucial component to curbing the drug addiction process. It is believed that modafinil may work so well at reducing drug cravings by targeting this very mechanism. Unlike many stimulant medications which can produce some type of "high" (especially if abused by snorting or injection, or taken at abnormally high doses), Modafinil has a low abuse potential, and offers several other advantages over methylphenidate.

Modafinil does have a relatively positive track record for mitigating substance abuse disorders. For example, the administration of Modafinil can attenuate cocaine dependence. In contrast, methylphenidate (Ritalin, Concerta, Metadate, Daytrana), while being very effective as an ADHD treatment, does little to curb comorbid substance abuse disorders in ADHD patients. Unfortunately, the effectiveness of Modafinil on treating comorbid substance abuse disorders in individuals with ADHD may be limited to specific drugs. For example similar positive effects of Modafinil on nicotine dependence appear to be less pronounced.

Modafinil may also offer advantages over traditional stimulants as well. As a cognitive enhancement type of pharmacological agent, modafinil may be useful in improving the work performance of adults with ADHD by improving short-term memory and visual recall, impulse control, and spatial skills (all of which are frequent deficits in children and adults with ADHD). Additionally, similar improvements were seen in individuals with schizophrenia, suggesting the diversity of modafinil's range of performance in cognitive improvement. These improvements are typically not seen in individuals unaffected by psychological disorders, further supporting the evidence that modafinil is less likely to be abused recreationally in the general population.

The potential implications of modafinil for ADHD treatment may be further reaching than the details outlined in the original article (and basis of this post, highlighting the effects of modafinil on amphetamine abuse in adult ADHD). For example, modafinil, as a vigilance-promoting medication, can offset an afternoon dip in arousal state (which has implications on many of the shorter-acting stimulant medications, which begin to wear off around this time). This may be useful for individuals with sleep disorders (which are common in ADHD), as well as regulating circadian rhythms. In a post earlier this month, we investigated the relationship between ADHD and seasonal affective disorders, and hinted at the association between ADHD and disruption in circadian rhythms.


Potential future implications of Modafinil as an ADHD treatment alternative:

Additionally, while Modafinil may offer benefits for the whole ADHD spectrum, this blogger hypothesizes that it may be most useful for treating the inattentive subtype of the disorder. Some reasons for this are as follows:

• Activity patterns and circadian rhythms may often be associated with ADHD subtype. For example, "morning people" with ADHD may have a tendency to fall into the more hyperactive/impulsive group, while "eveningness" is more of an inattentive ADHD trait, suggesting more of a disruption in the circadian rhythms of inattentive ADHD'ers.
• Additionally, non-stimulants often have somewhat of a better track record with the inattentive subtype of ADHD compared to the more hyperactive/impulsive subtypes. The uses of the non-stimulant atomoxetine (Strattera), highlight this general trend. While atomoxetine treatments often result in drastic improvements in all ADHD subtypes, negative side effects are often less seen in the inattentive subtype.
• Compared to stimulants, non-stimulant medications for ADHD often do a better job at not exacerbating comorbid disorders such as obsessive compulsive or anxiety disorders (which are often more common to the ADHD inattentive subtype). Additionally, Modafinil treatment can be useful in treating adults with ADHD and a history of mood disorders.
• Modafinil offers advantages over methylphenidate as far as fewer side effects including appetite suppression, sleep disturbances and heart rate dysfunction (orthostatic tachycardia, which essentially is significant changes in heart rhythms based on postural changes, such as standing up quickly from a seated position).
• Anecdotal evidence, as noted by the Modafinil and amphetamine abuse study mentioned earlier, also suggests that Modafinil may be a useful treatment method for "refractory" cases, or individuals who have consistently shown poor response to other treatment medications and interventionary measures.
  
• Finally, it is important to note (and this was also touched on in the Modafinil and amphetamine abuse study), that Modafinil treatment may be better suited for the more "controlled" abusers of stimulants. In other words, better effects might be seen for adults who regularly take illegal stimulant drugs such as amphetamines as a conscious effort to "self-medicate" for their ADHD, as opposed to an out-of-control drug addict who craves the drugs on a non-scheduled basis.

Given the high propensity of comorbid disorders when deciding on treatment for ADHD, as well as practicality issues concerning the administration of medicinal agents for treatment of the disorder in adults, I see a fair amount of potential for Modafinil's "off-label" usage as a treatment alternative to stimulants in adults with ADHD.

ADHD and Balance Impairment: Visual and Inner Ear Deficiencies

Balance dysfunctions and visual or vestibular deficiencies: Uncommon comorbids in the ADHD spectrum:

When we think of comorbid disorders to ADHD, we often envision disorders which can be diagnosed psychiatrically. Common examples such as depression, anxiety, Obsessive Compulsive Disorders (OCD), oppositional defiant disorders, and conduct disorders often come to mind. In addition, it is perhaps no surprise that learning disabilities are relatively common in children and adults with ADHD. If we do delve into physical comorbid disorders, things like Tourette's and tics may come to mind. For those skilled in the diagnosis and treatment of ADHD, even non-trivial comorbids such as bedwetting and sleep disorders may be apparent.

However, there is another impairment that often goes along with the ADHD population, especially in children. Sensory processing disorders are often seen in the ADHD population, especially in children. This includes more "physical" dysfunctions including the ability of the child to maintain balance and equilibrium. To the frustrated parent of coach of an ADHD child, this may introduce another complication with regards to sports or other activities which involve coordination and balance, such as basketball, baseball, tennis, soccer, gymnastics, musical instruments, dance, etc.

The aim of this post is to investigate and discuss impairments in balance function in children with the disorder, We will be citing and highlighting some key studies in the overlap between ADHD and balance dysfunctions (especially relating to functions derived from visual and tactile signals) and look for possible underlying causes and treatment methods:

Brain regions involved in Balance Dysfunction in the ADHD Child:

Most experts often cite specific "hot spot" regions of the brain for the ADHD patients. Among these, the prefrontal cortex part of the brain often receives the most attention. Less pronounced, however, are the studies associating the cerebellum, and their implications on ADHD. For a reference to the Prefrontal Cortex and Cerebellum brain regions, please consult the brain diagrams below:

Shown above is a human brain. The Cerebellum region, which plays a major role in governing balancing functions and may be compromised in a significant subsection of ADHD children, is shown in purple in the top picture. The area highlighted in orange in the bottom drawing roughly corresponds to the prefrontal cortex region of the brain, which plays a major role in impulse control. Deficiencies in blood flow and overall activity of this prefrontal cortex region of the brain are often seen in children (and adults) with ADHD, and may be responsible for some of the difficulties in filtering out comments and actions for appropriateness.

The inter-relationship between attention and balance/coordination: The strong association of the prefrontal cortex and cerebellum regions of the brain:

Many studies involving brain regions and ADHD often miss this connection. The relationship between these brain regions may go a long ways in explaining ADHD comorbid disorders as well, especially the more "physical" ones such as speech complications, developmental coordination disorders, etc. While perennial "hot spot" brain regions, such as the prefrontal cortex, are frequently mentioned in studies involving brain activity in ADHD, this particular brain region is actually intricately interconnected with the cerebellum (as well as another key brain region, the basal ganglia. The role of the basal ganglia in kids with ADHD has been discussed previously in other postings, but in general, the basal ganglia tell how fast a person "idles". 'Type A' personalities, such as workaholics, individuals with OCD and overly focused individuals typically have overactive basal ganglia, whereas many with ADHD often exhibit underactive basal ganglia.).

We have already mentioned that the balance-governing regions of the brain (the cerebellum) is interconnected with a key impulse-control region of the brain (the prefrontal cortex or PFC). We also mentioned that impulsivity is a characteristic of the Hyperactive-impulsive and Combined ADHD subtypes (as opposed to the more inattentive forms of the disorder). Interestingly, the prevalence of balance dysfunction cases seems to predominate in the combined subtype of ADHD (main paper as reference source). This correlation lends further credence to the hypothesis that the balance-governing and impulse-governing regions of the brain may be "co-affected" in the case of the balance-deficient, hyper-impulsive ADHD child.

Key points concerning balance related deficiencies and ADHD:

• ADHD is often associated with developmental delays. Indeed, studies highlighting a delay in cortical maturation in children with ADHD suggests that children and teens with the disorder may fall "behind the curve". By its own very nature, the vestibular system often does not fully develop until the age of 15, so immature development in this brain region may result in deficiencies in this system throughout almost the entire span of childhood in an individual with ADHD.


• Additionally, EEG and imaging studies have also demonstrated relative deficiencies in both size and activity (by measuring blood flow patterns) in various brain regions of ADHD children. These include the cerebellum and the caudate nucleus. Both are interconnected and associate with the "ADHD region" of the prefrontal cortex (PFC). This PFC region plays a major role in the impulse-control process and deficiencies in its function can result in a weak self-regulatory system of impulsive behaviors (which are hallmark characteristics of ADHD, especially in the hyperactive/impulsive and Combined subtypes).


• The cerebellum gathers input from visual, vestibular (inner ear), and somatosensory (mainly tactile senses, such as perceived through the skin and internal organs) systems. As we can imagine, a defect in one or more of these information-obtaining sensory systems, and the cerebellum (as well as the interconnected region of the PFC) may be compromised. Thus ADHD and sensory deficits may be intricately related.


• Taking this one step further, we may wish to explore the link between ADHD and sensory disorders, including processing disorders and sensory integration disorders. One thing is for sure, however: ADHD is not simply limited to deficits in the PFC!


• The vestibular system also plays a crucial role in what is known as "gaze stabilization" (i.e., stabilizing the focus on a particular fixed object when you yourself are moving). The very nature of "gazing" obviously has visual implications as well, so a deficiency in the vestibular component of gaze stabilization may also affect visual input success as well. Interestingly (an perhaps not surprisingly), visual input deficiencies are also seen at high rates in children with ADHD.
  
  This may actually serve as one of the key contributing factors as to why maintaining attention (to, say, a teacher), may be so difficult for ADHD kids, because they literally are having trouble focusing their visual attention (gaze) on their target of interest (i.e. a teacher standing up in class giving a lecture), especially if the child is already fidgeting around in their seat. In other words, there may be some inherent deficiency in this particular component of the attention span, and needs to be addressed further in the near future.

Investigating the sources of balance impairment in children with ADHD:
In order to clarify where I am coming from on this, I will highlight an extremely recent publication in the Journal of Pediatrics by Shum and Pang. This study investigated the different systems of balance in children, including somatosensory (balance governed by tactile features), visual, and vestibular (inner ear and the sense of equilibrium). They tested approximately 50 children (ages 6-12) with ADHD for balance discrepancies by isolating each of the three systems listed above to test sensory organizations of balance. A highlight of the study can be seen below:

Instruments/Methods of the study:

1. A platform which can induce a feeling of motion on a child who stands upon it (this disrupts the somatosensory component of balance, forcing the child to use their visual or vestibular functions to compensate for the somatosensory impairment).
2. Surrounding scenery which can visually give the illusion of motion. This forces the child to use their vestibular and somatosensory methods of equilibrium, as the visual sense is disrupted. Another variation of this is to have the child perform with their eyes closed.
3. A combination of the two methods above will isolate the vestibular component of balance, as both the somatosensory and visual sources of balance are now both compromised.
4. A total of six different environmental conditions were performed to isolate one or more senses of balance. The researchers noted which of the three modes of balance were most likely to be compromised in the ADHD children. The findings are highlighted below:
   

While balance-related issues can stem from visual discrepancies, somatosensory issues (i.e. the sensations of touch and pressure from the skin and even internal organs), and vestibular (inner ear) imbalances, it appears that ADHD children are most likely to suffer from visual imbalances. This is closely followed, however, by deficits in vestibular function. Somatosensory difficulties appear to occur in ADHD children as well, but the role of this system is likely to be much smaller than for the other 2.

Possible academic implications of balance dysfunction and ADHD: Does the source of an ADHD child's balance deficiency affect his or her sensory learning style? The following points are simply the result of this blogger thinking out loud. Nevertheless, these might be some good topics of future study, as balance difficulties may be useful in evaluating academic strategies.

• These findings on balance may even extend to the classroom and affect the learning environment of an ADHD child. Given the above, abnormalities in these areas may even affect a child's mode of learning and learning style. While these assertions simply remain personal hypotheses of this blogger, a child with visual discrepancies leading to balancing difficulties may also be deficient in visual perception and therefore struggle in a visual-dominated learning environment. He or she may gravitate towards a more auditory or kinesthetic style of learning.
  

• Conversely, it is also possible that vestibular-regulated balance dysfunctions, which stem from the inner ear may actually extend to a child's auditory learning capabilities. Again, this remains a hypothesis, but given the fact that severe childhood ear infections can affect both balance and hearing (as well as ADHD symptoms, see previous post on childhood ear infections and ADHD), a child with vestibular-related balance deficiencies may also have more difficulty in a predominantly auditory-based learning environment. This may spell bad news if an ADHD child's teacher engages in more auditory discussions or as the child moves up to high school and college courses where an auditory lecture is the more common form of teaching and communication.
  

• A double-whammy?: Given the fact that children with ADHD may suffer from both vestibular and visual (and even somatosensory) information processing for balance, it leads us to wonder if the child may also have learning deficits in 2 of the 3 major forms of learning (visual, auditory or kinesthetic). If this is the case, trying to accommodate an ADHD child's education could be extremely difficult, if he or she must heavily rely on only one predominant mode of acquiring and processing information.
  
  For example, if a child were to undergo a study similar to the one listed above, and it turns out that he or she is weak in both the visual and vestibular forms of balance, and (this is a big "if" and is only hypothetical at the moment) the whole balance governing/learning style hypothesis holds true, he or she may have to rely on a predominantly kinesthetic form of learning. While this child may succeed in hands-on learning subjects (i.e. frog dissection or wood shop class), he or she may have an exceedingly difficult time in other subjects such as algebra or history where hands-on-learning opportunities are more difficult to implement.
  
  

• The role of balance and sensory stimulation may have even greater-reaching academic implications. Another study just came out recently investigating the role of posture stability (i.e. how well a person stabilizes their center of balance) on ADHD and dyslexia. The study found that comorbid ADHD symptoms greatly influenced the effects of posture stability in dyslexic individuals, which may even have implications to affecting the reading environment of the individuals with dyslexia. It's important to keep in mind that this study involved adults instead of children, but the fact that ADHD may play such an integrated role into sensory modulation of other disorders into adulthood may signify the deep level of inter-relationship between cognitive function and sensory motor stimulation.
  

Vestibular Stimulation as an alternative form of ADHD Treatment?: As an interesting aside, there has been some pronounced effect on treating ADHD symptoms with a non-pharmaceutical alternative method called vestibular stimulation. We will be addressing the validity of these findings and their potential for practical usage in a later discussion.

ADHD and Seasonal Affective Disorder

ADHD and Seasonal Affective Disorder (SAD): Are they Linked?

Is it possible that ADHD is a seasonally fluctuating disorder? It sounds intriguing, but remember, for diagnostic purposes, classic ADHD symptoms such as hyperactivity, impulsiveness and inattentive behaviors (beyond the normal range of age-appropriate behavior) must persist for a set period of time (the typical cutoff is 6 months for most cases). Nevertheless, it is worth investigating whether there is any sort of seasonal pattern to the disorder. If there is, there could be far-reaching implications such as medication dosages (if diagnosed or initially treated during a "high ADHD symptom" period may result in effects of over-medication for the rest of the year, while initial dosing during a "low-tide" season of ADHD symptoms may prove inadequate in the later months).

Intuitively, we would probably assume that ADHD symptoms would be worst during the dark winter months, but is there any data to support this hypothesis? As it turns out, there may be. Here are the results of a few relevant studies on the apparent connection between ADHD and seasonal related psychological disorders:

• Seasonal Affective Disorder (SAD) symptoms overlap and co-exist at higher rates in those with ADHD: A study by Levitan and coworkers on seasonal affective symptoms in adults with ADHD found that the prevalence of seasonal affective disorders was higher in the ADHD population than in the general population. This study accounted for some of the obvious factors such as geography (someone in Seattle would be more prone to seasonal related disorders than, say, someone in San Diego).
  
  Perhaps not surprisingly, the rate of appearance of seasonal affective symptoms was higher in women with ADHD (in general, depressive-like disorders such as SAD are more common in women in general). However, other interesting comparisons were seen, such as the prevalence of seasonal affective symptoms in the inattentive subtype of ADHD (as opposed to the hyperactive/impulsive or "combined" subtypes of the disorder). While this subtype connection may be interesting, it is important to remember that comorbid depression is often seen more in the inattentive-dominant forms of ADHD than the hyperactive-impulsive forms of the disorder.
  
  
• Overlap in medication treatments for ADHD and SAD: While we should be careful not to simply lump a bunch of disorders together just because they share similar treatment methods, the relationship between SAD, ADHD and medications such as buproprion (Wellbutrin) may be worth noting. Bupropion has shown to be clinically effective in the treatment of a whole spectrum of disorders including seasonal affective disorders.
  
  Additionally, this medication has shown its far-ranging capabilities, due, in part to its success as both an anti-depressant and "pseudo-stimulant" (of course there is a heated debate among professionals as far as whether "Wellbutrin" should even be mentioned in the same sentence as "stimulant", but its unusual, and relatively unknown mode of action keep it from an exclusive anti-depressant label, at least in the classical sense).
  
  The reason I personally use the term "pseudo-stimulant" is that bupropion can function as a dopamine reuptake inhibitor (which is one of the major modes of action of several ADHD stimulant medications and is typically uncharacteristic of most anti-depressants which often predominantly target the brain chemical serotonin). This may be evidenced by bupropion's relative effectiveness in treating ADHD (please note that bupropion or Wellbutrin is still extensively used in ADHD treatment in place of a stimulant if there is some type of depressive related disorder, however, findings such as the one in this previous study seem to indicated that buproprion may be effective for treating free-standing ADHD without comorbid depression).
  
  While again, I should reiterate that similar treatment methods does not necessarily equate to similar disorders or conditions, the relative effectiveness of this medication for treating both disorders at least leaves the door open for the possibility that there exist similar underlying modes of action between ADHD and SAD.
  
  
• The connection between ADHD and circadian rhythms: While SAD, by definition is a seasonal (as opposed to daily) issue of cyclical patterns of time, it is worth mentioning that new research is being done with regards to differences in the chronological patterns in the bodies of individuals with ADHD. In other words, there may be an actual scientific explanation behind the reasons why your ADHD child likes to stay up until three in the morning on a consistent basis.
  
  There also appears to be an affiliation with daily rhythms and ADHD subtype. For example, while impulsivity is often more associated as a "morning" behavior, the inattentive subcomponent of ADHD appears to be more affiliated with the evening. This may factor into the differences in sleep patterns and prevalence of sleep disorders in ADHD children, and may even highlight the daily schedule differences between the ADHD subtypes.
  
  If the hypothesis that individuals with ADHD are at least partially predisposed to different patterns of circadian rhythms compared to the general population, it may stand to reason that these same individuals may also be more susceptible to seasonal fluctuations. Some studies confirm this possible "double" association of ADHD to both seasonal fluctuations and circadian rhythms.
  
  
• Overlapping treatment strategy of Light Therapy for ADHD and SAD?: There has been a recent surge of evidence that light therapy, when administered at the correct wavelengths, is an effective treatment for seasonal affective disorder (and often with measurable levels of success), may now be useful for treatment in the ADHD population.
  
  As an interesting aside, there may be some unusual side effects of ADHD stimulant medications with regards to light therapy. A case study of a single child noted that there may be a possible connection between methylphenidate and photophobia (photophobia referring to fear of or excessive sensitivity to the light). Of course this observation was limited to just one patient, but the correlation of the symptoms with methylphenidate treatment at least suggests the possibility that this is a possible (albeit) rare side effect of one of the most popular stimulant medications for ADHD currently on the market.
  
  Blogger's side note: it is also worth mentioning that this case report was also published by the same individual who brought us the interesting case study which became the topic of an earlier post in this blog: excessive talking as a potential side effect of methylphenidate treatment. I will refrain from making any comments or conclusions about this, but on a personal note, I actually enjoy reading about some of these unique side effect case studies of the popular drug, and wonder if this will result in an increased level of vigilance with regards to monitoring odd side effects of common ADHD stimulant medications in both clinical studies and individual prescriptions.
  
  
• Omega 3 (n-3) fatty acid deficiency: A common underlying factor for both ADHD and seasonal affective disorders? I saved what is perhaps the best explanation for last. It consistently has been shown that individuals with ADHD are often deficient in omega-3 fatty acids. We have even discussed the theory behind omega-3 fatty acid supplementation for ADHD in earlier bloggings. Now it appears that omega-3 deficiencies may disrupt circadian rhythms as well, possibly due to an impairment in melatonin production (melatonin is a hormone which is tightly associated with the sleep-wake cycle and hence has implications on the circadian rhythm patterns in a particular individual).
  
  This may suggest that omega-3 fatty acid deficiencies may either help cause, or exacerbate the severity of both ADHD and circadian rhythm impairments. Interestingly, there is some evidence that omega-3 supplementation may be beneficial in treating seasonal affective disorders as well. In fact, diets rich in omega-3's may be an underlying reason why seasonal affective disorders are relatively uncommon in Iceland, which, due to its far-northern location, experiences exceptionally long, dark winters.
  

While I admit that the evidence for the link between ADHD and Seasonal Affective Disorders is nowhere near as strong as for other ADHD comorbid issues (such as Tourette's, anxiety, conduct disorders, and learning disabilities), I still wanted to pass on some of the information out there supporting a possible link between the two disorders. Given the close associations both between depression and seasonal affective disorders, including the argument that SAD should be labeled as a specific subtype of depression, and the high rate of comorbidity between ADHD and depressive disorders, there is certainly a possibility that the magnitude of overlap between ADHD and SAD is greater than we might imagine.

Methylphenidate, Anxiety and ADHD: How do they fit together?

Effects of Comorbid Anxiety on Methylphenidate Treatment in the ADHD Child:

Medication with stimulants such as methylphenidate has consistently proven to be a popular and relatively effective mode of treatment for the ADHD child. However, questions arise regarding its side effects. In particular, the effectiveness of methylphenidate (Ritalin, Concerta, Daytrana, Metadate) can be jeopardized if the child with ADHD also has some type of comorbid disorder (such as depression, obsessive compulsive behaviors, Tourette's and a host of other common associate disorders) which may be negatively impacted by the ADHD treatment. Anxiety-related disorders are seen in up to 35% of ADHD individuals, according to some studies.

Typically, treatment is met with some type of adjunctive medication to treat the comorbid disorder (which can be quite tricky, as it introduces the problem of potential drug-drug interactions, as well as a possible impairment in the effectiveness of the ADHD treatment medication), a non-stimulant method of treatment such as Strattera (atomoxetine), or non-drug alternatives (behavior therapy, EEG, nutrition and dietary strategies, etc.). While isolated behavioral therapy has limitations for treating ADHD (especially in cases of "refractory" ADHD), it has proven to be a beneficial mode of treatment for childhood anxiety disorders.

In the case of anxiety disorders alongside ADHD, treatment with stimulant medications such as methylphenidate can also be tricky. However, recent findings seem to indicate that methylphenidate is a safe mode of treatment for ADHD with comorbid anxiety. However, a new publication notes that there may be a significant distinction between the effects of anxiety on methylphenidate's effectiveness from a behavioral standpoint vs. a cognitive standpoint. Let me explain further.

When attempting to determine whether a child should be diagnosed and treated as having ADHD, the supervising physician often gives out rating forms to both parents and teachers of the child in question. Numerical rating scales with regards to classic ADHD symptoms (i.e. impulsivity, hyperactivity, inattentiveness, etc.) comprise the majority of the rating forms, and these results are tabulated and typically used in the diagnostic process. Additionally, these rating forms are often administered after a specific period of time following treatment (with medication, nutritional therapies, counseling or ADHD coaching programs, etc.) to assess the effectiveness of these treatments.

While the level of agreement between parent and teacher rating forms is generally high, significant differences may often be seen. In other words, how a child's perceived behavior in the home may be notably different than his or her behavior in the classroom. While there are an array of possible factors and explanations for this, the presence of comorbid anxiety may be an important but often overlooked reason for this discrepancy.

In the study titled: Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety, the researchers found that the behavioral improvements in children with ADHD were similar regardless of whether the child also had an accompanying anxiety disorder. In other words, a notable decrease in symptoms of hyperactivity, impulsiveness and behavioral annoyances was frequently seen. Since these symptoms are often more of the obvious tell-tale signs of the disorder, it would be easy to conclude (especially from a parent's standpoint) that all is well again.

However, on the opposite side of the coin, the side dealing with the cognitive deficits of ADHD (which, not surprisingly have immense academic implications), may tell a different story. The study found that for the ADHD children without an accompanying anxiety disorder, methylphenidate treatment often contributed to vast improvements in their cognitive function (and subsequent academic achievement potential). However, if the ADHD child did have an accompanying anxiety disorder, the methylphenidate treatment was significantly less effective (and possibly even counter-effective). This may serve as a possible explanation for at least some of the variability between parent and teacher evaluations of the same ADHD child.

This leads to the question: does comorbid anxiety affect the cognitive ability-enhancing effects in all academic areas or just in some of the sub-fields of academic-related cognitive functioning?

The study investigated this by administering a Weschler Intelligence Test (WISC III) to the children and examined the effects of comorbid anxiety and methylphenidate medication on three subcomponents of the test: Coding, Arithmetic and Symbol Search. An explanation of the results in these three subcategories with regards to what they measure, possible implications of these subcategories, and the effects of anxiety and methylphenidate treatment are summarized below:

• Arithmetic: This is a timed test in which arithmetic questions are orally presented to the children and the responses are measured, assessing both speed and accuracy. Methylphenidate treatment produced a slight improvement in the ADHD children without comorbid anxiety. However, for the children with comorbid anxiety, the use of methylphenidate was ineffective (in fact, a slight decrease in performance was seen, but this was exceedingly small. It should be concluded that methylphenidate treatment had no reasonable positive effect for the ADHD children with comorbid anxiety for this particular subcategory).
  
  This should lead to an array of questions, including ones such as "does anxiety hamper one's performance in math, if one is ADHD (or even if one is not ADHD)?". Intuitively, we would expect the answer to be "yes", as evidenced by the huge number of children (and adults) who have self-reported "mathphobia". However, some well-reputed studies seem to indicate that methylphenidate treatment can actually help with mathematical abilities. Is there something else going on here?
  
  One potential explanation (not mentioned in the study) may reside in the possible presence of a third comorbid factor, such as an underlying comorbid auditory processing disorder. Auditory processing disorders are relatively common in individuals with ADHD, however, since the two disorders often exhibit symptomal overlap, comorbid auditory processing disorders are often missed in ADHD children.
  
  Interestingly, some recent evidence has come out that there may be a connection between auditory processing issues and anxiety disorders. This possible link between anxiety and auditory processing disorders has been addressed previously in another section of this blog. Note that the arithmetic subsection is administered orally in the WISC III test.
  
  If the theory that auditory processing difficulties are seen alongside anxiety disorders, it is entirely possible that the discrepancies in the ADHD with comorbid anxiety performances me be largely due to the nature of how the arithmetic portion of the test is administered. It would be interesting to see if any improvements were seen in the arithmetic scores were improved in the anxiety subgroup if the questions were presented in a written, non-auditory format.

• Coding: This section of the WISC III test measures skills involving visual-spatial coordination, speed and concentration. The individual (for those over 8 years old) is instructed to copy a line of code substituting a number for a symbol (this would involve something along the lines of writing, say, a "1" where a star is presented, "2" for a "circle", "3" for a smiley face, etc.). A high performance in this section has implications for advanced academic tasks that involve utilizing tables and formulas (think of solving chemistry problems using data from a periodic table at the top of the page, etc.).
  
  In addition, a strong visual-spatial aptitude may have implications for things such as note taking skills and the like. As a result, a strength in this area may be particularly useful in upper-level courses involving the sciences, foreign languages and anything that requires an individual to "decode" and translate new information quickly. With regards to the anxiety vs. non-anxiety ADHD groups, both showed some degree of improvement with methylphenidate treatment for this subsection.
  
  However, the non-anxiety group showed a significantly greater positive response (around twice as big of an increase in scores for this subsection following methylphenidate treatment as the comorbid anxiety group) to the methylphenidate treatment, suggesting that comorbid anxiety was a relative impediment to methylphenidate-mediated improvements in this area as well.

• Symbol search: This subsection involves picking out or identifying whether a particular symbol is present in a row of symbols. It has direct implications on one's ability to pay attention to detail as well as the ability to quickly scan through information to find what is relevant. Both the anxiety and non-anxiety groups showed slight improvements following methylphenidate treatment, however, once again, the improvements in post-methylphenidate scores were about twice as large for the non-anxiety group of ADHD children.

Of the 3 subtests, methylphenidate treatment helped the most in the coding section, had minimal effects in the symbol search section and little (for the non-anxiety group) to no or negative (for the anxiety group) effects for the arithmetic section.

Other studies have also investigated the effects of comorbid anxiety on cognitive task performance in ADHD children. By and large, it appears that memory-based tasks are the hardest hit by an accompanying anxiety disorder when methylphenidate is administered as an ADHD treatment. Other studies have confirmed this finding on anxiety disorders impeding memory enhancement via methylphenidate treatment. This seems to agree with the data on the coding section, which involves a type of working memory for the symbol deciphering process.

Based on what we have covered here, it would be reasonable to scrutinize significant differences between parent and teacher ratings and behavioral and attentive improvements for the possibility of an accompanying anxiety disorder to go along with an ADHD diagnosis in a child. While anti-anxiety medications can be useful, and co-administered with ADHD stimulant drugs under the watchful eye of a carefully trained physician, there is also evidence that

These findings suggest that comorbid anxiety can be a serious handicap to achieving cognitive and academic-related improvements in response to stimulants such as methylphenidate. However, please note that, based on the main study of our discussion on ADHD, anxiety and methylphenidate, notable behavioral improvements were seen from methylphenidate treatment in both the ADHD + anxiety and the ADHD minus anxiety groups.

The implications of this discrepancy can be noteworthy. To the parent who is only marginally involved with their child's academic progress, and is simply concerned with getting more manageable behavior out of their ADHD child, the sharp reduction of negative behavioral symptoms may lull the parent into a false sense of security that all is well on the home front. This stratified response to the methylphenidate medication may be lost to the unassuming parent.

However, it may be possible that an accompanying anxiety disorder (and maybe even an auditory processing disorder) may be lying there dormant to the oblivious parent. For the teacher, however, an improvement in classroom behavior due to medication, but a lack of improvement in academic work (especially in memory-related tasks) may be a tip-off that an undiagnosed accompanying anxiety disorder may be in place in this ADHD child. Thus this discrepancy in medication-derived improvements may actually serve as a potentially powerful diagnostic tool for detecting an accompanying anxiety disorder in a child being treated for ADHD.

ADHD, IQ and Gene Combinations

How combinations of 2 "ADHD genes" increase the risk of verbal IQ deficiency and behavioral disorders:

We have spoken at length on the matter of genes and their effects on the disorder of ADHD. The vast majority of the numerous ADHD gene studies we have previously discussed have looked at these genes in an isolated manner. However, it begs the question as to what the implications are of having more than one "ADHD gene". For example, does having 2 genes of the "ADHD form" double the risk of having the disorder? Quadruple it? What about having 3 or more of the "at risk" genes? Do certain specific ADHD genes have a dominating influence in the likelihood of inheriting the disorder?

A recent publication came out in the past few days examining the inter-relationship between ADHD, genetics, IQ and behavioral symptoms. It is worth noting that the two genes implicated in the study and their association with ADHD are ones we have previously discussed, the Dopamine Receptor 4 gene, (DRD4) and the Dopamine Transporter 1 gene (DAT1).

ADHD gene #1: DRD4: This gene, called the DRD4 (short for dopamine Receptor gene 4) is located on human chromosome #11. In addition to its association with Attention Deficit Hyperactivity Disorder, this gene is also believed to be associated with schizophrenia, alcoholism and drug abuse, Parkinson's (namely a resistance to this disorder, associated with a specific form of the gene), mood disorders, and novelty-seeking behaviors (which have obvious implications to the impulsive nature of ADHD). Additionally, the proteins coded for by this specific genetic region appear to be major targets for the antipsychotic drug clozapine.

ADHD gene #2: DAT1: This gene, called DAT1 (short for Dopamine Transporter gene 1) is located on human chromosome #5 (in the p15.3 region of the chromosome to be specific, if you are not familiar with this terminology, this is simply a more specific location on the 5th human chromosome). This gene also goes by the name SLC6A3 or simply DAT (without the "1"). Like the DRD4 gene mentioned above, the DAT1 gene has also been implicated in ADHD as well as a number of other disorders. These include (but are not limited to): Tourette Syndrome, cigarette smoking (interestingly, this includes a form of the gene which apparently offers "genetic protection" against the risk of nicotine dependence), bipolar disorders, substance abuse and Tourette Syndrome.

**Blogger's note: The fact that so many psychological and behavioral disorders are also believed to be connected to genes associated with ADHD is simply not a matter of coincidence, especially in this blogger's personal opinion. The majority of the disorders listed above are frequently seen alongside ADHD as comorbid disorders. While no one can deny that environmental factors do play a critical role in the development of these disorders, it is worth repeating the fact that certain individuals, because of the forms of these two (as well as several other "ADHD genes") inherently have at least some degree of genetic predisposition to these inter-related disorders.

Childhood externalizing behaviors:

Childhood externalizing behaviors cover a wide spectrum of behavioral disorders. These include behaviors such as excessive aggression, antisocial behaviors towards peers or authorities, defiant behaviors (in excess of the typical range of expected age-dependent behavior range), excessive hyperactivity, conduct disorders, etc. These should not be confused with the more "internalizing" behaviors, such as anxiety and related disorders. With regards to ADHD subtypes, the externalizing behaviors such as conduct disorders are often more likely to be seen with the hyperactive-impulsive and combined ADHD subtypes, while the internalizing childhood behaviors such as anxiety are more frequently affiliated with the inattentive subtype of ADHD.

IQ: Although IQ is often thought of as one specific number which hovers around 100 for the majority of the population (i.e. 110, 97, etc.), it is actually comprised of multiple subcategories. Generally, the scores in each of these subcategories also generally centralize around 100 and most individuals scores show slight to moderate differences between the subcategory scores. However, in the case of most learning disabilities, this is not the case. Typically, children and adults with learning disabilities have average or above average scores in many of the IQ subtypes, but often have glaring deficits in one or more areas, in which the IQ for that particular area is significantly lower than the rest. In the case of this study relating IQ, externalizing behaviors and the DAT1 and DRD4 genes, the particular IQ subtype most in question is the verbal IQ.

The study found some interesting points with regards to IQ, externalizing behaviors, and the 2 "ADHD genes" (keep in mind that when we are talking about these genes, we are only talking about specific forms, or alleles, of these genes, which are seen only in a fraction of the population. For reference sake, the "at risk" forms of the two genes are referred to as the 7-repeat allele for the DRD4 gene and the 10-repeat allele for the DAT1 gene. Don't get caught up too much in the specifics, these "repeat" describe specific DNA patterns that are seen in these "at risk" forms of the DRD4 and DAT1 genes). The results can be summarized in the following points below:

• For ADHD children who had only the "at risk" DRD4 (but not the DAT1) gene form, there was no significant increase in the likelihood of having a low IQ or behavioral disorders.


• Likewise, for the children who only had the "at risk" DAT1 (but not the DRD4) gene form, there was no significant reduction in IQ or increased risk of behavioral disorders.


• Additionally, the actual correlation between low IQ and increased risk of deviant behaviors (which is often seen in multiple other studies, especially with regards to the IQ and criminal behavior link), was not observed if the child only had one of the two "at risk gene forms" either for the DRD4 or DAT1 genes.


• However, for ADHD children who had both the "at risk" forms of DRD4 and DAT1 (please note that this study investigated children who had inherited these gene forms from both parents, i.e. they had 2 copies of each "at risk" gene) showed a significant level of association between low verbal IQ scores and increased likelihood of having increased expression of externalizing behaviors.


• It is also worth mentioning that the IQ/behavior connection was only seen in the verbal IQ subcategory and "externalizing" behavioral subcategory. In other words, other forms of IQ (such as more "performance" ones such as motor coordination and kinesthetic types of intelligence) and "internal" behavioral disorders (such as anxiety-related disorders), were apparently not factors affiliated with either of these gene forms.

These findings potentially highlight the complexities of disorders such as ADHD, behavioral disorders and personal characteristics such as genetics, and may also explain some of the incongruities between studies. For example, if one particular genetic study finds a specific form of a certain gene to be associated with ADHD, another one will typically find there to be no genetic linkage (even if the studies are conducted in the same manner with similar study numbers, subjects, and experimental methods).

This may be due to the fact that most of these psychological, behavioral, and functional connections are associated with multiple genes and do not pop out unless more than one "at risk" gene forms are in place. In other words, multi-gene analysis studies (although much more difficult to conduct and analyze) may be our best bet for finding the real genetic basis for ADHD occurrence and related behaviors. This may stress the fact that gene-gene interactions may be as powerful as gene-environment interactions for assessing the risk of an individual acquiring attentional and behavioral disorders such as ADHD.

ADHD Gene Falls Inside Reading Disabilities Genetic Region

ADHD and learning disabilities are often seen alongside each other (many actually label ADHD as a learning disability itself, but most of the medical community considers ADHD a separate entity). Now there is some evidence that ADHD and reading related learning disabilities may be genetically linked:

A quick background of genetics: The human body consists of somewhere around 30,000 to 50,000 genes (the numbers actually vary, as actual genetic regions are not fully pinned down, and various regions of DNA called pseudogenes, exhibit genetic qualities themselves). These genes are spread across 23 pairs of chromosomes (one copy per each pair), and have a relatively wide degree of diversity among individuals. These genes are essentially lined up nearby each other, such as houses in a neighborhood. When the genes are transmitted from parent to offspring, the closer two genes are to each other, the more likely they will be passed on together. Thus if an individual has an "ADHD gene" form located right next to, say a gene which has certain forms which increase one's susceptibility to color blindness (this is just a hypothetical example), we would likely expect a greater than normal co-occurrence of ADHD and color blindness.

The ADHD gene in question is often referred to as the Protogenin Gene, located on the 15th human chromosome. If falls in a region flanked not only by what is considered a genetic region implicated for reading disabilities. In addition, this gene is also believed to aid in the physical developments of the nervous system and neuronal cells at the embryonic stage of life.

While these findings are preliminary, they suggest a possible genetic factor for the connection between ADHD and reading disorders (of course we should not overlook the obvious fact that having attentional or concentration difficulties also has a negative impact on one's reading capabilities, especially if required to read complex material for long periods of time). It also lends credence to the growing body of evidence that suggests the role of developmental delays in the onset of ADHD.

ADHD and Handwriting: What's the Connection?

The link between ADHD and Poor Handwriting (Dysgraphia):

It has been well-known for years that individuals with ADHD are often more prone to problems with penmanship, that is, they have trouble producing legible handwriting. But why is this the case? There are several theories out there, and multiple studies showing how effective ADHD treatments can also result in major improvements with a person's handwriting. I will review some of the current findings on the topic:

1. A group in Israel sought to investigate whether the problem with handwriting in ADHD children was due more to underlying language problems (i.e. spelling, formulating sentences, etc.) or more due to the mechanical problem of the physical writing process. While they concluded both were at play, the results of their study seemed to indicate that underlying language difficulties played only a secondary role to the writing difficulties and that the primary cause was due to "non-linguistic deficits". Interestingly, the group did find specific patterns to the frequent mis-spellings of words, instead of a host of random, unrelated errors. This blogger personally found the conclusion of the article's summary to be particularly amusing, as it recommended a "judicious use of psychostimulants".
   
   
2. Continuing on with the "judicious use of psychostimulants" theme, we must investigate the effectiveness of one of the most common types of stimulants for ADHD, methylphenidate (Ritalin, Concerta, Metadate). This drug has elicited a number of positive effects as far as improving both the cognitive and physical aspects of handwriting, as concentration or attentional lapses subside, allowing the thought process and physical act of writing to be performed simultaneously.
   
   However, another study found that even medication with methylphenidate had its limits, and that handwriting gradually deteriorated as the child continued with the writing process. This suggests that for long essays or standardized tests (such as the writing portion of the SAT's, or A.P. exams), medication with methylphenidate or other stimulants may only be useful early on.
   
   
3. Specific Genetic Factors may underlie both ADHD and handwriting problems: There was an interesting study done by a Dutch group which suggests that there may be some sort of genetic factor that inhibits fine motor movements (such as those required for writing) which then make their way over to ADHD. In other words, this study seems to suggest that ADHD is a secondary problem to fine motor problems such as dysgraphia (typically, it's the other way around, where ADHD is considered the primary disorder). This study discovered that non-ADHD siblings (who, by definition, share half of the ADHD child's genes, provided they are not identical twins) of the ADHD children also had difficulties with more complex forms of the writing process, compared to the general population. In other words, these siblings had some degree of impairments with the writing process, but not to the degree of their ADHD siblings.
   
   This suggests that these non-ADHD siblings may have enough genetic "impairments" to share some of the comorbid writing problems as their ADHD counterparts but not enough to manifest an outright diagnosis of ADHD themselves. In other words, the comorbidity (co-occurrence of) ADHD and dysgraphia is apparently not an all-or-nothing phenomena.
   
   
4. Differences in hand-eye coordination and motor control problems are more pronounced in the left hand for ADHD vs. non-ADHD children: We have previously investigated key brain regions commonly associated with ADHD, including differences in relative brain region size, use of brain regions, bloodflow patterns, brain electrical activity patterns, sense of smell, the relationship to alcoholism, brainwave patterns, and genetic differences targeting specific brain areas.
   
   However, it is worth noting that these brain regional differences are often not laterally symmetric, that is they may only be on the left side or right half of a particular brain region. This lopsidedness may play a role in manual dexterity and motor coordination differences between ADHD and non-ADHD individuals, which appear to be even greater in the left hand (which, in most cases the non-dominant one).
   
   The article which found this discrepancy between the different sides of the body goes on to suggest that testing for fine motor coordination in ADHD kids would be better suited for the left hand, since the effects are more pronounced. This leads to this potentially intriguing question: If handwriting is done with the dominant hand, does it stands to reason that handwriting difficulties are just the tip of the iceberg with regards to immensely greater fine motor difficulties? In other words, if an ADHD child is having trouble writing with his or her dominant right hand, how bad would the fine motor deficits be if they needed to use their left hand for something like catching a baseball, or shooting a left-handed layup in basketball?
   
   Based on this finding, it appears that poor handwriting may be just one aspect of a much larger fine motor disability. Another possibility, however, is that using one's non-dominant hand requires a higher order cognitive process than utilizing one's dominant hand for a routine task. This possibility may actually carry some weight, as we have seen in previous posts how discrepancies between ADHD and non-ADHD individuals begin to balloon as the cognitive processes become increasingly more difficult.
   
   This also seems to jive with the underlying genetic component of these disorders proposed by the ADHD sibling study in the previous point, in which the non-ADHD siblings had trouble only with the higher-order writing processes and not the more automatic ones (such as doing a simple task with one's dominant right hand). Unlike the Israeli study, this seems to favor more of an underlying cognitive discrepancy as the main culprit of poor handwriting in ADHD, as opposed to a more "mechanical" one.
   
   
5. The genetic discrepancies in ADHD and fine motor impairments may be one of motor timing: Going back to the genetic aspects of ADHD and motor impairments such as dysgraphia for a moment, it is worth mentioning another finding by a group investigating difficulties in timing fine motor applications in ADHD children. This study utilized tests such as pressing a button on self-determined one second intervals (and measuring how close the child's perceived timing matched up with "real" one-second intervals), tapping one's finger as many times as possible within a given time limit (a relatively common test for individuals with ADHD and related disorders) and tests which measured reaction timing to moving objects and visible changes (which may have direct implications as to how well a child would perform in a sport involving reacting to moving objects, such as baseball, lacrosse, or tennis). Based on these tests, the authors concluded that the motor impairments in the ADHD children were more likely due to timing issues as opposed to generalized motor problems.
   
   As a blogger's note, this might explain some of the difficulties in the handwriting mechanics, such as crossing "t's" and dotting "i's", which essentially involves hitting a "target" on the paper, or keeping up with a teacher while taking notes (which is a very time-dependent process which often requires a fast execution of handwriting numbers, letters, diagrams, and symbols).

A number of books on the subject of ADHD and writing disorders show actual handwriting samples of children on and off medication for ADHD. The differences are astounding. Additionally, differences in complexity and eloquence in creating stories are often extremely pronounced depending on the mode of expression. For example, actual cases involving gifted children with ADHD have highlighted how a child can concoct an thorough, detailed, and well-rounded story orally, but when asked to write out the same story, he or she is scarcely able to construct even a single, legible, coherent paragraph.

This brings up the important issue as to whether children with ADHD should be afforded opportunities to use different modes of communication for their assignments, such as dictating or typing as opposed to handwriting. It appears that for many, the actual process demanded of ADHD children for actually writing may rob or ferret away the majority of their cognitive capacity, resulting in a barren landscape of creativity or eloquence.

Given the fact that many children with ADHD respond positively to alternative learning or expressive styles such as predominantly auditory (dictating) or kinesthetic (typing) means of expression, numerous questions surrounding the degree of accommodation for these ADHD children must be addressed. It is my personal hope that the findings of some of these studies will shed some light onto the mechanical and cognitive impairments of the physical writing process for children with ADHD will help shape an educational environment to help these children to flourish.