Childhood Ear Infections and ADHD: Why the link?

When we scan the literature for statistics on ADHD and search for early warning signs or tip-offs that a young child may be prone to the disorder, a few common trends seem to pop up again and again. One of these is the high rates of ADHD and attentional difficulties in kids suffering infection of the middle ear (Otitis Media) in early childhood.

During early childhood, the actual positioning of the ear canal is still adjusting, the pathway into the middle part of the ear is actually at a flatter angle than in a mature adult. This difference in positioning actually makes younger children much more prone to ear infections than older children or adults. Unfortunately, these infections may increase the risk of further complications down the road, including an increased onset of attentional difficulties, including ADHD. Here is what some of the literature has to say about the ADHD/ear infection connections:

Relationship between middle ear infections and inattention: The basis for inattentive ADHD?

The main culprit for attentional deficits is often believed to be the result of hearing loss (even mild), early in a child's life due to complications with the middle ear, including infections, allergy-related causes or build-up of fluids in the canal. As a result, the child begins to miss out on verbal cues, and does not develop the same level of response to an adult voice. Auditory deficiencies (including auditory processing disorders) may stem from this key development period, even if the hearing difficulties are only temporary.

Not surprisingly, there is a wealth of data associated with hearing loss due to middle ear complications can lead to language processing difficulties. We have seen how auditory processing disorders can often occur as a comorbid factor in ADHD, and may be linked to seemingly unrelated behaviors including comorbid anxiety and conduct-related disorders.

It is important to note, however, that other early childhood studies have not seen a link between infection and attentional difficulties (observed by parents, teachers, or clinicians).

Interestingly, environment may play a huge role in explaining this discrepancy between study results. One study found that children who had middle ear complications early on along with poor home environments were significantly more likely to develop attentional difficulties (along the lines of what would be classified as ADHD). Therefore, the effects of early ear infections on compromised attentional difficulties may be significantly reduced if a supportive home environment is maintained for a child. This is good news for parents of children with ear infections. But what about the hyperactive component of ADHD?

The link between hyperactive behaviors and middle ear complications: The basis for hyperactive/impulsive or combined subtype ADHD?

While it seems more intuitive that ear infections could lead to auditory problems and subsequent attentional difficulties (especially to auditory cues), the relationship between ear infections and hyperactivity is less inherently obvious. This association would be more relevant to the hyperactive/impulsive and combined subtypes of ADHD.

For over 30 years, researchers have linked high rates of ear infections and hyperactivity (this study used the term "minimal brain dysfunction", a phrase which this blogger has personal objections, nevertheless, it is a relatively common term in the literature). Later studies confirmed these findings, including one which reported the majority of children medicated for hyperactivity had a past history of 10 or more childhood ear infections. These numbers were in sharp contrast to the prevalence of ADHD in non-hyperactive children.

One thought may be that ADHD which includes a significant hyperactive component (as opposed to the more inattention-dominated form of the disorder) is more likely to be associated with comorbid disorders that correspond to ear infections. We have seen previously that comorbid disorders to ADHD are often related to particular subtypes.

For example, anxiety and depressive-like symptoms are often more likely to co-exist with primarily inattentive ADHD, while conduct disorders are more likely to co-exist if there is a high hyperactive/impulsive behavior (especially in the combined subtype). In general, the prevalence of more severe learning disabilities is often more associated with the inattention-dominant form of ADHD, while motor tics are more likely to be a hyperactive/impulsive trait. Carrying these associations in mind, are the studies linking early ear infections to hyperactivity simply due to associations with hyperactive subtype-dominated comorbid disorders?

One particular study found that children with hyperactivity vs. children with learning disabilities (and not hyperactivity, remember, learning disabilities are often seen at higher rates in the inattentive forms of the disorder) had similar numbers of total childhood ear infections. However, the timing of the infections did seem to matter. Children with hyperactivity experienced more recent ear infections (within the previous year) compared to the learning disability kids.

In other words, the question surrounding hyperactivity and ear infections may be more of a "when" question than a "how many" question. This may also suggest the possibility that hyperactivity due to middle ear troubles may be more of a temporary condition (this is supported by trends as an individual with ADHD ages, typically, the hyperactive symptoms of the disorder begin to subside as a child gets older and reaches adulthood, while the inattentive symptoms are more likely to plateau) as opposed to inattentive problems stemming from ear infections. Severity of the infections may also be a triggering cause or associated warning sign of an increased risk of developing hyperactive behaviors. The same study found that earaches and upper respiratory tract infections were higher in the hyperactive group than in the less-hyper learning disability group.

So what's going on with the connection between ear infections and ADHD-like hyperactivity?:
Although none of the above studies mentioned this possibility, as a blogger I have a few ideas on the subject. One of the most probable reasons for the ear infection/hyperactivity correlation may be due to the treatment process of ear infections. Let me explain:

Ear infections are typically treated with antibiotics. While these drugs work wonders for most infections, they also can disrupt the healthy bacterial counts in the digestive tract (that is, they kill off many of the "good" bacteria in our digestive systems in addition to the "bad" bacteria which may be causing our infections).

If the "good" digestive bacterial counts fall too low, the digestive process is compromised. The absorption and digestion process may suffer, as key nutrients may now be compromised (even if no major dietary changes occur). We have spoken extensively about nutrient deficiencies and ADHD as well as ADHD-related nutrition strategies in earlier posts.

Additionally, if good bacterial counts fall low, incomplete digestion results, which can lead to byproducts such as higher concentrations of organic acids, as well as incomplete breakdowns of potential allergens (which can increase sensitivity to food allergens, among others). These allergens and acids can actually begin to penetrate the blood brain barrier and show up in higher concentrations in the brain. Neurological disorders, including abnormal hyperactivity may actually be triggered by digestive imbalances (to a degree beyond what most of us realize). We are just beginning to recognize the huge degree of inter-relationship between the nervous and digestive systems, including brain-gut interactions.

There has been a longstanding "hot" discussion surrounding food allergies and ADHD (as well as possible connections between food allergies and disorders like fibromyalgia and chronic fatigue syndrome), and the disrupted bacterial balance in the digestive system due to frequent antibiotic usage for recurrent ear infections may be a governing factor. This seems to make sense, especially considering the fact that hyperactivity was more linked to recent ear infections (and resultant antibiotic treatment), while the more inattentive behaviors and learning disorders seem to be a more long-standing symptom. Since bacterial counts begin to re-stabilize following antibiotic treatment (if a proper diet is maintained), the food-related hyperactivity may begin to subside, but for recent infections and treatments, the digestive bacteria may still be imbalanced, triggering an onset of ADHD-like hyperactive behaviors.

Of course this is just the blogger's personal hypothesis, but it at least seems plausible that the actual treatment for ear infections may play an equally strong role on the high rate of occurrence between ADHD and ear infections.

Ginkgo biloba for ADHD: A natural herbal treatment alternative?

A few weeks ago, I discussed the merits of ginseng for treating ADHD. What I did not mention is the fact that this special herb often works even better in tandem with another important "brain herb", Ginkgo biloba. It's benefits also extend beyond the nervous system, and the Ginkgo has been used to treat everything from increasing blood flow to Alzheimer's to glaucoma to hormone replacement to protection against neuronal degradation. While somewhat wary (personally) of using generalized "brain booster" nutrients for ADHD (it is a highly variable disorder of complex etiology and treatment methods), I am interested whenever new research publications arise on the topic. Just this week, a new paper came out on the merits of Ginkgo biloba as an ADHD treatment option.

Here are some of the major points of the publication:

• Irritability is an often overlooked side effect of ADHD. Medications, especially over-prescription with stimulants such as methylphenidate and amphetamines can increase this unwanted side effect. However, Ginkgo exhibited a positive mollifying effect on irritability for the individuals in the study.
  
  
• While one of the knocks against Ginkgo biloba is that it can sometimes result in sedative effects, the study found these to be extremely mild. However, to go along with the irritability-reducing benefits above, Ginkgo was able to improve the individuals' tolerance for frustration (to the degree that this behavior could be measured).
  
  
• We have seen previously that oppositional defiant behaviors are often comorbid to ADHD (which can often manifest themselves alongside seemingly unrelated disorders such as auditory processing disorders or even bedwetting). One of the strongest suits of Ginkgo biloba may actually be in curbing these oppositional behaviors. This suggests that Ginkgo may be effective for the more Hyperactive/Impulsive or Combined Subtypes of ADHD, where comorbid oppositional behaviors are more often seen (as opposed to the predominantly inattentive subtype of the Disorder).
  
  
• Nevertheless, Ginkgo biloba appeared to boost symptoms of attention and working memory as well. This may suggest Ginkgo's versatility, and that it could be used universally across the ADHD "spectrum", including for the 3 classic or traditional subtypes of the disorder.
  
  
• The study highlights the relative success for co-treatment with methylphenidate and clonidine for individuals with ADHD and comorbid anxiety disorders. The authors suggest a functional comparison between Ginkgo and clonidine, and hint at its use as an alternative to clonidine/methylphenidate treatment (of course, it is also possible that Ginkgo may be used alongside lower doses of stimulant medications, which could be very useful in reducing unwanted side effects, which are often mild for low doses of stimulants, but typically begin to appear with greater frequency when stimulant dosing is increased). Thus, Ginkgo could possibly act as a side-effect-saving alternative to higher doses of medication.
  
  
• As a precautionary measure, due, in part to some of its anti-clotting properties, there is some concern about Ginkgo triggering internal cerebral bleeding. Indeed, other studies have also addressed this possible concern, highlighting issues such as haemmorrhage risks, as well as herb-drug interactions with Ginkgo and anti-coagulant medications.
  
  
• Keep in mind the extremely small nature of the study (only 6 individuals) should be met with healthy skepticism. However, the results were still notable. Statistically significant reductions in some of the trademark ADHD symptoms (fidgeting, restlessness, inattention, etc.) upon Ginkgo biloba treatment definitely highlight its potential as a more "natural" alternative treatment method for ADHD.
  

Why the Menstrual Cycle may affect ADHD Medication Dosing Levels

Do hormonal fluctuations result in variable ADHD medication dosage levels across the menstrual cycle?

We have investigated the impact of gender on ADHD in a number of earlier posts. We have covered topics such as:

• Gender Based Metabolic Differences in ADHD brains

• Gender Dependent ADHD Genes, including MAOA, SLC6A2, SLC6A4 and COMT

• ADHD subtypes and Comorbid Disorders

Clearly, there are a number of boy/girl differences in the root causes, diagnoses and treatment methods for the disorder.

However, we need to investigate whether intra-individual differences are also an important factor, especially where medication treatment and medication dosing levels are concerned. Based on a number of studies, it appears that women may actually require different medication dosing levels depending on where they are in their menstrual cycle. Additionally, post-menopausal drugs such as estradiol patches may also alter the drug effects of certain ADHD medications such as amphetamines. The main culprits are most likely fluctuating levels of estrogen and progesterone.

Here are brief summaries on some of the relevant studies and their findings. Wherever possible, I will include a link to the original studies:

• The link between Estradiol treatment and amphetamine medications: This study focused on whether pretreatment with estradiol played any role in the reaction to amphetamines. The drug used in this study was D-Amphetamine, which would correspond to the medication Dexedrine, however, this is also the predominantly active compound in medications such as Adderall or Vyvanse (once this "pro-drug" is metabolized). It is unclear at the moment whether chemical "cousins" to amphetamines, such as methylphenidate (Ritalin, Concerta, Daytrana, Metadate), also exhibit these fluctuations when combined with estradiol-releasing drugs.
  
  The study found that for females who took estradiol-supplementing treatments during the early follicular phase (pre-ovulation) of the menstrual cycle experienced an overall greater "stimulating" effect of the amphetamine medication (taken as 10 mg of amphetamine). This may suggest that a slightly lower dosage during this stage of the menstrual cycle might be warranted, and (as this blogger's personal hypothesis) may actually affect the addiction potential of ADHD stimulant drugs such as amphetamines.
  
  
• Another study by the same group found that estrogen may be responsible for some of the heightened euphoric effect felt from amphetamine-based drugs. However, the hormone progesterone may actually counteract some of this euphoria. During the luteal phase of the menstrual cycle (after ovulation), high levels of both estrogen and progesterone are seen (although levels of both of these taper off going into menstruation), so the effects of estrogen may be curbed. During the late follicular phase, where progesterone levels are low and estrogen levels begin to spike, the "high" may be at its peak, especially if stimulants are involved.
  
  
• A case study found that an increase in inattentive symptoms coincided cyclically with the menstrual cycle for a patient who was undergoing treatment for newly-diagnosed ADHD with a twice-daily dosing regimen of the stimulant medication Concerta.
  
  
• The findings from these two studies suggest the possibility that a slightly smaller dosing schedule with amphetamine-based ADHD medications (such as Adderall, Vyvanse or Dexedrine) may be warranted during the follicular phase. However, during the luteal phase, when progesterone levels are higher, the amphetamine-based effects are less pronounced. This may correlate to a slightly higher dosing regimen for amphetamine-based treatment for ADHD and related disorders.
  
  
• While there is a relatively good theoretical basis for this assertion above, practical consideration measures must also be considered. Based on the relative scarcity of studies (besides the 2 mentioned above) on the amphetamine-menstrual cycle interactions, it is unclear as to how pronounced the medication change should be.
  
  For instance, should someone taking 10 mg of Adderall during the follicular phase boost up to 15 mg for the luteal phase? 20 mg? 30 mg? Additionally, hormonal fluctuations vary during the phases themselves, such as the estrogen spike during the late follicular phase. Questions abound, especially when dealing with the brief ovulatory phase as well.
  
  

This blog post hopefully introduces what may be a new consideration to women who have ADHD and are currently taking stimulant-based medication treatments. Perhaps this posting simply confirms what you have already experienced.

Nevertheless, given the fact that administering variable levels of medication based on cyclical patterns such as time of day (like ramping up methylphenidate concentrations via controlled release formulations to offset "acute tolerance" based effects), and the fact that individuals with ADHD may experience seasonal variations in symptoms, at least suggests, that variable dosing of medications across the near-monthly period of the menstrual cycle may prove to be beneficial treatment strategy for females with ADHD.

Long Wave Infrared Imaging: A new detection method for ADHD?

Detecting ADHD using the long-wave infrared spectrum:

I always enjoy covering new breakthroughs in the diagnosis and treatment methods in the medical field. A new study just came out which may have a number of potential applications to aid in the diagnostic process of ADHD, which I believe is worth sharing. Called Long-Wave Infrared Imaging, this method utilizes the infrared spectrum to detect biological activity (namely bloodflow patterns) via the differences in radiation emitted by these activities. The study, titled Sensitivity and Specificity of Longwave Infrared Imaging for Attention-Deficit/Hyperactivity Disorder, found that this method may be a surprisingly powerful way of separating ADHD from other related disorders, aiding in the always-difficult process of differential diagnosis.

The basics of Long-Wave Infrared Imaging:

The term "long-wave" is a relative term, of course, referring to wavelengths of approximately 10 nanometers (or only one one-hundred millionth of a meter). Differential bloodflow patterns can result in temperature differences by a full degree (Celsius), making this technology useful in tracking bloodflow disorders. A recent publication in the Journal of Medical Physics by Bagathaviappan and coworkers suggests describes how this long-wave infrared imaging can detect areas in the circulatory system where bloodflow activity is sluggish or reduced. Typically, these areas appear "cooler" on the spectrum, due to the lack of a new, replenishing blood supply.

Applications for ADHD:

A number of studies have confirmed the hypothesis that individuals with ADHD have reduced bloodflow levels marking a recuction of activity to multiple key brain regions. Additionally, while several disorders have a number of overlapping symptoms (which can make the diagnostic process more complicated, especially if multiple comorbid disorders are present), differential blood flow patterns to the brain may be able to help make these distinctions. For example, blood flow patters to the brains of ADHD and OCD (Obsessive Compulsive Disorders) can show pronounced differences, which can aid the diagnostic process between these two disorders (while ADHD and OCD are often considered to be on "opposite" ends of the spectrum with regards to neuro-chemical signaling levels, these two disorders can often exhibit similar symptoms, such as a severe impairment in the response to verbal directions. This is especially true in younger children).

This technology may even be extended to measuring or predicting which medications may work for an individual diagnosed with ADHD, based on blood flow in specific localized brain regions. Cerebral blood flow patterns may help predict the response to common ADHD drugs such as methylphenidate (Ritalin, Concerta, Metadate, Daytrana). For example, a study by Cho and coworkers found increased blood flow in at least three different brain regions for individuals who showed poor response to methylphenidate treatment compared to their peers who did show improvements under the drug.

While the medication response study was done utilizing a different type of brain imaging device known as SPECT, which utilizes gamma rays and radioactive tracers to detect brain activity in 3-dimensional patterns. While SPECT has proven to be an extremely powerful and effectively safe method of detection (the radioactive isotope used in this method is relatively non-invasive and breaks down quickly, and the gamma rays are carefully controlled), concerned parents may still have an inherent fear of the terms "radioactivity" and "gamma rays" tend to shy away from this powerful detection method on their kids.

While this blogger personally has a very high opinion about the use of SPECT as a diagnostic tool for ADHD and related disorders, it is at least worth mentioning the possibility that long-wave infrared imaging methods may be a viable alternative method in at least some of these imaging cases (SPECT technology has been around for over 30 years, but the recent advances in computational power resurrected this technology in the very recent past, similar possibilities may abound by this infrared technology, which has been around even longer).

Keep in mind that the studies utilizing this range of infrared imaging technologies for detecting and differentiation disorders such as ADHD are still relatively scarce. Nevertheless, long-wave infrared imaging appears (at least in this blogger's personal opinion) to be a powerful diagnostic tool for ADHD and related disorders in the near future.

ADHD and Seasonal Affective Disorder

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

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

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

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

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