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.

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.