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.

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.

Bedwetting ADHD Kids and Depressed Dads: Is there a connection?

ADHD and Bedwetting (Nocturnal Enuresis): How are the two related?

There is a relatively recent publication that came out within the last couple of weeks on the relatively high rate of occurrence in bed wetting (enuresis) among ADHD children, which I believe is worth sharing. We have previously investigated this ADHD and bed wetting connection (note that bed wetting may be more likely to be seen alongside the inattentive subtype of ADHD). However, this study offers some additional insight into this strange association between the two disorders. Here are some important points worth mentioning:

• Overlapping Drug Treatment for ADHD and bedwetting: It stands to reason that if a particular drug or agent is effective in treating multiple disorders, there may be a distinct possibility that those two or more disorders may share some type of underlying cause(s) or defect(s). For example, Tofranil or Imipramine, a drug used to treat enuresis and depressive disorders can possibly be useful as a treatment option for ADHD. We have also investigated the potential role of Reboxetine as a potential ADHD treatment in previous entries. Some work has found Reboxetine to be useful in treating therapy-resistant enuresis as well.

• Prevalence of Enuresis in ADHD: Enuresis refers to urinary incontinence which is limited to the night-time. Additionally, the term is typically limited to individuals over the age of 5 (i.e. a 3-year-old child who frequently pees in their pants would not be considered as suffering from enuresis, at least in the context of this study). The article cites other studies in which the rate of bedwetting (enuresis) in ADHD is as high as 30%, although other studies have it down around 10-20%. Still, compared to the general population, (factoring in things such as the age of the child, of course)the high rate of bed wetting in ADHD is especially noteworthy. There is some evidence from other studies that ADHD and enuresis may be more intricately linked than previously imagined. For example, one particular study has shown that treating urinary incontinence has a higher rates of failure in children with ADHD vs. non-ADHD children.
  
  
• The role of Oppositional Defiant Disorder (ODD) on Bed wetting: The study examine several different psychiatric disorders which frequently occur alongside of (or are comorbid to) ADHD. These include depression, anxiety disorders, obsessive compulsive disorders, tic disorders, nail biting, bruxism (teeth grinding), conduct disorders and oppositional defiant disorders. However, out of all of these different disorders which often appear alongside ADHD, the only one which exhibited a statistically significant correlation to increases in bedwetting was oppositional defiant disorder. Interestingly, oppositional defiant disorders have been associated with bedwetting in other ADHD studies.
  
  As its name suggests, Oppositional Defiant Disorder is a disorder in which a child exhibits disobedience, irritability and hostility towards authority figures beyond the range of normal age-appropriate behaviors. Of course there is a significant gray area with regards to what is age appropriate, especially when the child's environment is considered. Nevertheless, Oppositional Defiant Disorder (or ODD) is much more than just routine temper tantrums. Oppositional Defiant Disorders may also be associated with auditory processing issues and ADHD. It is somewhat interesting that anxiety disorders, which have also been correlated to oppositional behaviors, did not elicit a significant positive correlation to bed wetting.
  
  
• The autonomic nervous system as a potential underlying cause of ADHD, bedwetting and Oppositional Defiant Disorders: The autonomic nervous system is the part of the nervous system responsible for involuntary muscle actions such as digestive processes, blood vessel contraction, etc. It is subdivided into the sympathetic and parasympathetic nervous systems, which often act in a sort of "push-pull" opposition to each other. For example, the sympathetic nervous system does things such as boosting heart rate and constricting blood vessels, while the parasympathetic nervous system is in charge of activities such as reducing heart rates and relaxing sphincter muscles (which plays a role in bladder control).
  
  Typically, the sympathetic and parasympathetic components of the nervous system are kept in balance, but this balance may be thrown out of whack and result in numerous disorders. For example, it is believed that the parasympathetic nervous system is over dominant in cases of Oppositional Defiant Disorders (ODD). The study found that for ADHD and Oppositional Defiant Disordered children, functions such as heart rate were controlled excessively (if not almost exclusively) by the parasympathetic portion of the nervous system (while non-ODD and non-ADHD children had both sympathetic and parasympathetic controls operating on their heart rates. This suggests a common underlying imbalance among the different components of the nervous system which is common to ADHD and ODD individuals and often separates them from the non-ADHD'ers. Interestingly, other studies have indicated that bedwetting or generalized incontinence problems may also be caused by an overactive parasympathetic nervous system, which suggests that ADHD, ODD and night-time bedwetting may all share some underlying causes within the nervous system.

• Connection to Parental Depression: I personally found this observation to be interesting. The study found that the prevalence of bedwetting in ADHD children was higher if the father (but not the mother) of the child was suffering from some sort of major depressive illness. The article did not express an opinion as to whether these depressive symptoms were due in part to the child's bed wetting problems or whether there was some underlying mechanism at work.

• ADHD medications may Influence Enuresis: The authors highlight some other works in which popular ADHD medications may either increase or decrease the risk of bedwetting in ADHD children. For example, the article highlighted a case study (by the same author) in which treatment with methylphenidate induced nocturnal enuresis. Methylphenidate is one of the most common ADHD drugs, and often goes by the common trade names Ritalin, Concerta, Metadate and Daytrana (the patch form of the drug). Of course this is based on only one individual case, but for those of you who have read this blog on a frequent basis, will know that I like to report on some of these abnormal occurrences (for reference sake, here is an earlier blog post I have done on the possible connection between methylphenidate and excessive talking. While based on an isolated case report, I believe that this zany potential side effect was at least worth a mention). On the flip side, however, the non-stimulant alternative ADHD drug, Atomoxetine (Strattera) can be a useful treatment for enuresis. This blogger would personally like to see additional studies on whether ADHD children with a comorbid bedwetting condition actually saw a better reduction in their ADHD symptoms while on Strattera than while on methylphenidate. If this were the case, then bedwetting may actually served as a useful tip-off as to which type of ADHD medication would work best for that particular child.

Strattera (Atomoxetine) response may be affected by SLC6A2 gene

About a month ago, we were discussing the ADHD gene SLC6A2. Located on the 16th human chromosome, different variations of this SLC6A2 gene are believed to play at least somewhat of a determining factor as to the genetic predisposition towards attention deficit hyperactivity disorders (ADHD). We saw that this gene was also correlated to anxiety and depression-like symptoms (which commonly occur along many ADHD patients) and that these genetic factors were slightly stronger in girls.

Atomoxetine (Strattera) is a non-stimulant alternative to medication treatment for ADHD. Unlike most stimulant medications, which interfere and regulate the pathways of the neurotransmitter dopamine, atomoxetine acts upon the pathway of the neuro-signaling agent norepinephrine. While dopamine-related stimulant medications for ADHD can worsen accompanying anxiety and depressive-like disorders (extreme caution is necessary when prescribing stimulants if a severe co-illness of anxiety or depression is present alongside ADHD), Strattera has shown to extremely beneficial in the co-treatment of depressive-like illnesses, especially when used alongside the SSRI class of antidepressant drugs.

A recent publication in the journal Neuropsychopharmacology highlights the potential connection between variations of the "ADHD gene" SLC6A2 and the effectiveness Strattera (Atomoxetine) for treating ADHD.

It is important to remember that for most genes, there are slight variations in the different forms within the human population. For most, these small changes in DNA do not result in any major physiological differences, but for some, even a change of one or two units of DNA can make a huge impact on biological functions, such as response to a specific medication. We have previously discussed how both the Catechol O-Methyltransferase (COMT) and CREM genes, may both dictate different dosing levels for ADHD medications.

Based on the SLC6A2 and Strattera study, it appears that individuals with specific gene variations of the SLC6A2 gene had a significantly more positive response to atomoxetine (based on a common behavioral rating process typically used to assess ADHD and related disorders), than were others with different variations of the gene. These effects were seen even when another gene (the CYP2D6 gene, located on the 22nd human chromosome and is responsible for the metabolism of atomoxetine/Strattera) was taken into account.

We will hopefully discuss these findings in more detail later, but the main point to drive home from all of this is the concept of how individual gene variation (i.e., which specific forms of a particular gene one has), can play a major role in predicting whether:

1. An individual will even respond to particular drug (such as Strattera for ADHD), and
2. Whether that individual's particular forms of these genes predispose him or her to requiring a higher (or lower) than normal dosage level than otherwise physiologically similar individuals to achieve the desired effects.

This blogger personally believes that we have just begun to scratch the surface in investigating the power of gene-medication interactions, and how these interactions will shape the landscape for ADHD treatment.