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.

Treating ADHD with....Mirrors?

Using mirrors may help ADHD kids retain focus in school-related tasks:

One of the major goals of this blog is to examine as many different treatment methods as possible for ADHD, with the hopes of informing individuals with the disorder and parents and teachers of ADHD children to allow them to make the best possible decision for them and their child. This search has brought me to some interesting treatment methods, including the one described below. We will be examining the theory and potential effectiveness for the use of mirrors in treating ADHD. The majority of this information comes from a 1998 study done by Zentall, Hall and Lee, entitled Attentional Focus of Students with Hyperactivity During a Word-Search Task.

Please note: Psychology and behavioral modification strategies are not my personal forte, this blogger's strengths typically lie in the chemical, genetic and physiological aspects of ADHD and treatment of the disorder. Nevertheless, I was so intrigued by this paper, I have decided to give my best stab at reviewing the study and explaining the effects and overall practicality of its findings.

Some major highlights of the study are as follows:

• Earlier studies suggest attempts to regulate ADHD behaviors using self-control methods often fail. This is likely due to a number of factors, such as the relative differences in ADHD children to be motivated by delayed rewards or gratification (although I personally have seen several cases to the contrary. At my school, we offer a special ski trip which must be earned by behavior, and a number of kids, including those with ADHD are able to modify their behavior to remarkable degrees to earn a trip five weeks away. Nevertheless, rewards of less magnitude, especially ones further down the road have often been largely ineffective, at least based on my personal experiences). However, physiological studies do suggest some sort of absence or difference in the intrinsic reward system and motivation in ADHD children.
  
  
• Instead, ADHD children typically respond better to external stimuli, either good or bad. In other words, a child with ADHD will often show an improvement in response if he or she can see his or her behaviors or actions partly regulated from an outside source.
  
  
• The use of mirrors is geared towards this externally-driven stimulus method, by allowing the ADHD child to observe or see themselves from a third-person perspective. They are essentially taking cues from an external source in lieu of self-regulating their behaviors. In other words, they may perceive reinforcements better from the "child in the mirror" than internal reinforcements from themselves.
  
  
• The study even hints that children with ADHD may have a type of delay in the development of self-awareness. While this blogger's opinion is currently neutral on the validity of this assertion, the fact that neuro-developmental and cognitive delays are so prevalent in children diagnosed with ADHD, it is entirely possible that the rewiring and brain maturation processes responsible for developing a mature sense of "self" may also be behind the curve age-wise in ADHD children. If this is the case, then we would expect the mirror trick to lose effectiveness as the child ages and finally develops this sense of "self".
  
  
• Boosting states of arousal, including through the use of emotional states has been shown to increase a child's attentional focus. Several theories for hyperactivity, such as those by Zentall, support this assertion, claiming that excessive activity (beyond the perceived age and gender-appropriate amounts) may be a way for the child to achieve these heightened levels of arousal necessary for the performance of cognitive tasks, including school work.
  
  If this is the case, attempting to merely calm this hyperactivity via behavioral or pharmaceutical treatment may, in essence, be detrimental to the ADHD child, as it robs him or her from achieving a state of arousal necessary to achieve the desired state of focus. This may even play a significant role as to why a number of children with ADHD are predominantly kinesthetic learners (as opposed to the more "passive" auditory of visual learning styles). **Please not that the previous two italicized statements are simply personal opinions and musings of the blogger at the moment, however, note the potential effects that medication may have on this mirror treatment at the bottom of this post.
  
  
• Numerous adult studies confirm what may seem intrinsically obvious (but relevant to our current discussion): the presence of external "observers", including an audience, cameras, or even mirrors, significantly increase attentional focus (and subsequent self-control) in the individual being observed. However, limited study has been done on this phenomena in children. Nevertheless, it appears to make inherent sense that a child who is under the "watchful eye" of someone (even if that someone is their personal reflection in a mirror), may exhibit higher levels of attentional behaviors.
  
  
• The study highlights a work by Carver and Scheier called Attention and Self-regulation: A control therapy approach to regulating human behavior (1981) in which the use of mirrors increased the effectiveness of academic-related methods such as copying letters (which has practical uses in note-taking), persistence in problem-solving tasks (which has direct uses in academic areas such as math and science), and the extent of response generation exercises (which have direct implications in brainstorming activities and subjects such as creative writing assignments). Thus, the possible benefits of mirror usage are far reaching for the ADHD child.

• The experiment comprised of giving both ADHD and non-ADHD children a word puzzle (which was unsolvable, as a handful of the words the child was instructed to find did not exist in the puzzle. The children were notified of this fact, but were not notified on the number of words that were missing. When the child believe that he/she had found all of the words in the word search, he/she notified the experimenter and stopped the task. In other words, this study was tailored to track attention and persistence for a particular task). Both the ADHD and non-ADHD children worked on the puzzle in either one of two conditions: in front of a mirror (approximately 2 feet by 3 feet in size, on a wall in front of the table where the child was performing the word-finding task), or without a mirror.

• ADHD children showed noticeable improvements when working in front of the mirrors (i.e. finding more words). In contrast, the non-ADHD children who worked in front of mirrors were either unaffected or showed decreased levels of performance on the word finding task.

• Additionally, the study examined when a child looked up at the mirror or ignored it. It appears that looking up at the mirror improved the performance of the ADHD group but either did not effect or decreased the effectiveness of the non-ADHD'ers. Therefore perception of being "watched" appeared to improve the focus of the ADHD group, but may have overwhelmed the non-ADHD group. Interestingly, several of the ADHD children who were placed in front of the mirror but did not look up at it had significantly lower levels of performance than those that did look at the mirror. The study suggested that these children may have already developed strong "internalizing" behaviors of self-focus, such as vivid daydreaming.

• These findings may be interesting, due to a number of reasons. In previous posts, we have recently alluded to the fact that a particular region of the brain called the basal ganglia, which essentially governs how fast an individual "idles" (i.e. a "type A personality" such as a workaholic, obsessive-compulsive individual typically has higher basal ganglia activity, while individuals with ADHD often have lower levels of activity in this brain region).
  
  The basal ganglia activity is also increased when there's a sudden change in external stimuli, especially when the sudden change is perceived as dangerous or harmful. Under conditions such as these, the basal ganglia can become so overwhelmed, that the individual temporarily "freezes". Under a highly unpredictable or stressful situation (such as witnessing a traffic accident, crime or heart attack), ADHD individuals are often the first ones to react to the situation. It is believed that this is due to the fact that they have lower baseline levels of activity than their non-ADHD counterparts, and therefore have more capacity to accommodate to this new-found stress before either freezing up or becoming overwhelmed.
  
  Tying this in with our mirror discussion, the difference in response to the feeling of being "observed" by the mirror, may be due, at least in part, to heightened basal ganglia activity, which may begin to overwhelm the non-ADHD group but help optimized the basal ganglia activity in the ADHD group of children. This assertion remains the blogger's personal hypothesis, and was not mentioned in the study, however, I believe that there is sufficient groundwork to warrant a mention of this possibility.

• The results of the word-finding task may extend into other academic areas as well. The authors cited another study in which mirrors used as part of a larger classroom setup experiment (such as music, color settings, activity breaks, etc.) significantly improved performance, accuracy and completion on math assignments.

• Finally, there was a small side-study involving children who did not fit into either the ADHD or non-ADHD group (often due to medication). It appears that for the medicated group, the presence of the mirror was actually detrimental to performing the word finding task at hand. Therefore, the combination of mirror and medication for ADHD, especially in the academic or classroom setting, needs to be further investigated.

ADHD, Methylphenidate and Blood Sugar Levels

ADHD medications may interfere with blood sugar levels and glucose metabolism:

When we think of common side effects of ADHD medications (especially of the stimulant variety), we often consider things such as cardiovascular risks (increased heart rates and blood pressure), appetite suppression (which may subsequently result in temporary growth impairment), interference with sleep, dampening of creativity and emotions (i.e. taking on a zombie-like state), irritability, moodiness, and the like.

However, it appears that another equally important, but often less-considered side effect of many ADHD medications is a change in blood sugar and glucose metabolism. The first part of this post will investigate some of the research out there on the effects of common ADHD medications on brain glucose metabolism. The second half will zero in on some of the general metabolic differences between the ADHD brain and the non-ADHD brain, and will also investigate possible effects of age, gender and co-existing disorders:

1. A drop in blood sugar following methylphenidate treatment: A case study involving a diabetic woman who underwent a surgical operation for a brain tumor. While we cannot make any logical conclusions about the population based on one individual of unique needs, the fact that a pronounced drop in blood glucose (over 25%) following methylphenidate treatment is at least worth noting. It is unclear as to whether the effects were due merely to the methylphenidate (common forms of this drug include Ritalin, Metadate and Concerta), or rather to a drug-drug interaction.
   
   
2. Methylphenidate reduces required brain glucose amounts to perform cognitive tasks: A study done at the National Institute of Drug abuse found that the administration of methylphenidate reduces the amount of glucose (the brain's desired energy source) needed to perform a thinking task. It is believed that this lower energy requirement is mainly due to less "wasted" energy from a constantly wandering and side-tracked mind, such as one seen in individuals with ADHD.
   
   Interestingly, this same study also found that during non-cognitive tasks, the differences in brain energy requirements did not change with or without the drug. This may at least call into question the merits of ADHD stimulant medication usage if higher order cognitive tasks are not required. Furthermore, if the brain is already focused, the utilization of methylphenidate may even be overkill. The authors concluded that this may be a primary reason why adverse effects in concentration and focus can be seen when methylphenidate is administered to "normal" functioning brains.
   
   
3. Methylphenidate's influence on brain metabolism may be regio-specific: Another study done by the same author as in study #2 found that the effects of methylphenidate on brain glucose metabolism may depend on individual subregions of the brain. For example, this study found that for the basal ganglia region of the brain (this brain region essentially governs how fast a particular individual's brain "idles"), the relative activity of this brain region was typically reduced following methylphenidate treatment, compared to activities in other brain areas. This may be a bit counter-intuitive, since basal ganglia activity is typically lower in individuals with ADHD and higher in individuals with obsessive compulsive or anxiety-ridden behaviors.
   
   However, other brain regions such as the frontal and temporal regions of the brain (which are responsible for filtering out unimportant external stimuli and inhibiting impulsive behaviors, and, perhaps not surprisingly, often show lower levels of activity in the ADHD brain), experienced a boost in metabolic activity following methylphenidate treatment. It is believed that these responses are modulated through categories of receptors for the brain chemical dopamine (called Dopamine D2 receptors, which help control levels of this important neuro-signaling agent, which is often deficient in key regions of the ADHD brain).
   
   In this blogger's opinion, this dual action of inhibiting impulsivity (which can potentially dampen creativity) and shutting down some of the basal ganglia activity may actually be a reason why "zombie-like" behaviors are sometimes seen in children medicated or overmedicated with stimulants for ADHD.
   
   
4. The "Energy Deficient" Hypothesis of ADHD: While still in the hypothetical stage, there is a fair amount of evidence suggesting that ADHD may be due, in a large part, to a lack of energy to specific neurons in key brain regions such as the prefrontal cortex (part of the "frontal" regions of the brain discussed in the past point). This ADHD as an energy-deficiency hypothesis carries that astrocytes (star-shaped cells that provide energy and nutrition for growth and repair of neuronal cells) may be starved of some of their important nutritional needs for glucose and related nutrients. As a result, they are unable to effectively "feed" the neurons in these key brain regions associated with governing attentional and impulsive behaviors in the brain. Should this hypothesis hold true, it would stand to reason that regulating and improving glucose levels either via either medication-manipulated, or alternative dietary methods may help offset some of the energy deficient imbalance in ADHD. Some natural supplemental options to boost glucose levels in the ADHD brain may include ginseng and carnitine.
   
   
5. Reduced brain metabolism in teenagers with ADHD: The results of this study on metabolic differences in teenage ADHD brains agree with many of the findings discussed in point #3 above. This study investigated the effects of an auditory-based attentional task on rates of brain glucose metabolism in adolescents with ADHD. It found that there was minimal differences between glucose metabolic patterns in the brains as a whole when comparing the ADHD and non-ADHD individuals.
   
   However, it is also worth mentioning that in other related studies on brain metabolism in teens with ADHD, it was found that metabolic deficits were seen at significantly lower levels throughout the brain as a whole. Interestingly, according to the second study mentioned, these differences in brain metabolism were only seen in the girls with ADHD and not the boys, which suggests possible gender-specific differences in the etiology of the disorder.
   
   However, upon investigating for the more hyperactive forms of the disorder in the first study (remember that ADHD behaves as a spectrum, in which some individuals have the predominantly inattentive symptoms, while others exhibit the hyperactive and impulsive symptoms more readily, these different predominant features are typically grouped together as unique subtypes of ADHD), it was found that the hyperactive component of ADHD corresponded to a significantly reduced level of glucose metabolism in the whole brain. This brings up the question as to whether these metabolic differences exhibit any sort of subtype-dependent effects with regards to ADHD.
   
   Also, as in point number 3 above, metabolic deficits were apparent in more specific brain regions such as the left frontal lobe regions of the brain. Even more remarkably, there appeared to be somewhat of a sliding scale with regards to the relationship between reduced glucose metabolism and increased symptom severity in this particular "hot spot" (the left frontal lobe) region of the ADHD brain.
   
   The following sidenote is a personal comment by the blogger regarding some of the methods of the previous study. As mentioned above, the test for this adolescent ADHD study involved an auditory based attention task. However, as discussed in earlier posts on this blog, we have seen that auditory processing disorders sometimes accompany ADHD.
   
   Furthermore, due to a high degree of symptom overlap, a comorbid auditory processing disorder can often be missed in an ADHD child or adolescent. Because of this, we should not rule out the possibility that comorbid auditory processing issues may interfere with the results of studies such as this one.
   
   We can see that auditory processing takes place in multiple regions throughout the brain, many of which do not have significant overlap with the "ADHD brain regions". One would expect the brain of an individual with an auditory processing disorder to work harder to achieve the same results as that of a non-auditory disordered individual. Thus, a confounding processing disorder could, in theory result in an increased demand for energy utilization to the portions of the brain responsible for stimulatory processing, which could leave less available energy for the frontal lobe regions of the brain responsible for modulating hyperactive and impulsive ADHD behavior. These assertions remain hypothetical at the moment, but this blogger feels that the presence of undetected comorbid disorders can easily skew the results of these metabolic studies on the ADHD brain.
   
   
6. Age-Dependent Decline in Brain Glucose Metabolism in Adults with ADHD: Apparently, metabolic differences in ADHD brains are not limited just to children, adolescents, and young adults with the disorder. Some of the findings of this following study may seem inherently counterintuitive at first. While ADHD symptoms often decline as an individual with the disorder ages, we would expect that an accompanying level of improvement in glucose metabolism in ADHD-specific brain regions would hold true. However, according to this study on brain glucose metabolism in older ADHD adults, it appears that the opposite is actually the case.
   
   The authors hold that the decrease in glucose metabolism may actually be markers of a more efficient process of brain metabolism (i.e. these older ADHD brains may somehow conform to an efficient energy-conservation state allowing them to function more optimally, thereby decreasing the prevalence of ADHD symptoms), although this finding is somewhat suspect in this blogger's personal opinion.
   
   As an interesting side note, the decrease in brain glucose metabolism in adults is apparently gender-specific, according to the study. This parallels the findings from some of the adolescent ADHD brain metabolic studies. The notable metabolic decreases were observed in women with the disorder to a much larger degree in men. The authors of the study suggested this may be due to hormonal influences, such as changes in post-menopausal women.
   
   Given the anecdotal evidence supporting the association between ADHD and higher onsets of neurodegenerative diseases later in life, this blogger finds the results of this study to be of particular interest. There may even be some claims that genetics may be partly to blame for the overlap between ADHD and neuro-degenerative diseases. For example, a gene referred to as DAT1 (short for dopamine transporter gene 1, located on the 5th human chromosome) may be connected to both ADHD and parkinsonism (a secondary or alternate form of Parkinson's disease). DAT1 also helps regulate dopamine function, (although via a different method than the dopamine receptors mentioned in point #3), by coding for an enzyme that helps transport or shuttle dopamine into and out of neuronal cells. We have discussed these dopamine transporter genes in earlier posts.

We have covered a number of works on the metabolic differences of glucose in the ADHD brain, and how they differ from the brains of non-ADHD individuals. There is the distinct possibility that stimulant medications used to treat ADHD, such as methylphenidate (Ritalin, Concerta, Metadate, Daytrana) can significantly alter brain glucose requirements. It appears that significant differences in brain glucose utilization patterns and efficiency may affect the entire brain, but certain ADHD "hot spot" regions of the brain may be particularly hard-hit. It is unclear whether this is due to preferential metabolic differences of the ADHD brain (compared to the "normal" brain), or whether it is due to an all-out brain energy shortage.

It is also worth noting that significant gender-specific factors may also affect this process, with ADHD girls in particular showing the greatest metabolic deficits. It also appears that these effects are also being observed across the lifespan of the ADHD individual. Finally, there is at least a hypothetical possibility that sensory processing difficulties or other comorbid disorders commonly seen alongside ADHD may also play a role in these metabolic differences of ADHD brains.

Can ADHD be Treated with Ginseng?

The Theory Behind Ginseng as an ADHD Treatment Option:

Ginseng is well-regarded for its memory boosting, sleep improving, and brain-saving longevity benefits. In a general sense, it appears that it would be a good potential treatment method for ADHD and related disorders. Although successful clinical study publications on the specific use of ginseng for ADHD are relatively scarce, it appears that on at least a theoretical basis, this popular herb could work for treating ADHD and related disorders. I would like to highlight some of the biochemical and physiological reasons supporting its use as an alternative treatment for ADHD:

1. Compound diversity in ginseng: Ginseng is not simply one isolated compound, such as an individual drug, but rather a mixture of substances of potential pharmaceutical benefit. Among these are a family of compounds called ginsenosides. One of the underlying benefits this (and herbal treatments in general), is that many of these related compounds can work together in a synergistic fashion, nature's own alternative to drug cocktails. Given the fact that absorption, metabolism and utilization of biochemical agents for the treatment of disorders is rarely due to one isolated substance of pharmaceutical value, this multi-compound treatment method certainly has potential advantages over a single-drug treatment method for ADHD or related disorders.
   
   
2. Ginseng, dopaminergic activity, and ADHD: It has been demonstrated that herbal extracts of ginseng can exhibit activities that target the dopaminergic (dopamine-related) pathway and can exhibit neuro-protective benefits for these pathways. This is important, because ADHD is often chemically characterized by deficits in this pathway, which typically include reduced dopamine levels in the regions between neuronal cells throughout various key regions of the brain (ones that, among other things, are responsible for attention span, screening out irrelevant stimuli, and impulse control). There are even implications that ginseng compounds can accelerate the neurodevelopment process from stem cells.
   
   
3. Boosting of "synaptic plasticity": During the learning process, a certain amount of "agility" is necessary in the regions in between the cells as the brain begins to rewire itself to conform to the newly learned material. The ability of neurons to form new connections is referred to as synaptic plasticity. It appears that ginseng contains several key elements which helps maintain this "pliable" learning-friendly state. Essentially, compounds isolated from ginseng can moderate long-term potentiation, (long term potentiation refers to a learning and memory process in which communication between two neuronal cells is improved or made more efficient by stimulating both cells at the same time. This plays an important role in the development and maintenance of long-term memories). Given the fact that learning disabilities are frequently seen in ADHD (often more on the inattentive side of the ADHD spectrum), it stands to reason that ginseng may be useful in some of these comorbid learning-related deficits as well.
   
   
4. Ginseng boosts aerobic glucose metabolism in the ADHD brain: The ADHD brain typically contains deficits of glucose and oxygen (as determined by multiple imaging and brain scanning studies) in many of the key brain regions which modulate attentional control, impulsivity, and concentration. It is even postulated that ADHD may be an "energy deficient syndrome". Brain metabolic studies indicate that aerobic glucose metabolism is typically improved in the presence of ginseng isolates. Not only does this reduce some of the potentially brain waste products associated with oxygen-deprived brain activity, but this enhanced aerobic form of glucose metabolism in the brain is a more efficient process.
   
   
5. Ginseng may boost dopamine and norepinephrine levels: As mentioned previously, individuals with ADHD are typically deficient of the important neuro-signaling agent dopamine in key regions of the brain. However, a deficiency in another important neuro-signaling agent called norepinephrine is also frequently seen in the ADHD brain. Imbalances of both dopamine and norepinephrine are seen in ADHD patients, and can lead to disruptions in physiological processes such as attention span, complex cognitive processes, auditory processing delays, and motor behavioral dysfunctions. It is believed that the ginsenoside compounds (see point #1) may help alleviate some of these ADHD-related symptoms by boosting levels of dopamine and norepinephrine in these key brain regions, several of which are affiliated with ADHD.
   
   Interestingly, many stimulant meds for ADHD work by boosting levels of these same two compounds, meaning the effects of ginseng may approximate those of a stimulant medication used to treat ADHD. We will see in the next post how another natural brain supplement, Ginkgo biloba, may better approximate the action of non-stimulant ADHD medications. It is also worth noting that isolates of ginseng and ginkgo may work in tandem to boost memory and other related functions.
   
   On a side note, fatty extracts of the ginseng plant have been used to alleviate the dopamine-dependent "high" of cocaine, which supports the use of ginseng as a potential treatment agent for cocaine addictions. Similar results support the use of ginseng for treating nicotine addiction as well. This further validates the dopamine-dependent regulatory benefits of ginseng and its ability to stabilize fluctuations in neuro-signaling agents of relevance to ADHD.
   
   
6. Ginseng may protect against brain damage from excess iron: I have personally advocated the use of iron for treating ADHD in several other posts. It can counteract toxic effects of lead and other metals, improve the synthesis of dopamine from the dietary amino acid tyrosine, and improve sleep quality in ADHD children. However, there are several dangers associated with excessive iron supplementation, one of which is neuronal death and neuro-degenerative diseases such as Parkinson's. However, there is some evidence that ginseng can counteract this iron-related neuronal damage by regulating specific iron-transporting proteins in the brain. If these findings hold true, then ginseng might be of use as some type of "insurance measure" against potential damage from excessive amounts of iron supplementation designed to treat ADHD.
   
   
7. Promote nerve growth in brain regions typically under-developed in ADHD: We have reported earlier on some of the delays in maturation and development of specific brain regions in ADHD. Some research suggests that ginseng compounds may promote neuronal growth and development in the early stages of life. While currently a bit of a stretch, findings such as this may lead to the use of ginseng compounds to offset ADHD-associated neurodevelopmental delays somewhere down the road.
   
   
8. Neuroprotective effects of ginseng for the aging ADHD brain: This may be especially relevant to adults with ADHD as they age. In addition to its ability to help with neuronal cell development in the early stages of life (mentioned in the previous point), evidence suggests that the active ginsenoside "Rd" compound in ginseng can alleviate inflammatory damage and death to neuronal cells. Given the fact that early neurodegenerative effects are often present in ADHD-like mammalian systems, these results at least suggest that ginseng may be a potential life-long treatment option for individuals diagnosed with ADHD.