Does Lead Exposure Cause ADHD?

Many of these findings were based off of an original journal article regarding prenatal tobacco and lead exposure and the onset of ADHD by Braun and coworkers in the December 2006 issue of the journal Environmental Health Perspectives. For a quick synopsis of this article on lead and ADHD, please click here. Interestingly, this same group also published more recent papers on the effects of lead on conduct disorders, which are often comorbid to ADHD cases. This should be especially relevant for pregnant or nursing mothers. For more information on ADHD and pregnancy, please check out the collection of posts on this blog addressing the topic, which can be found here.

While the relevance of several studies regarding the effects of lead on ADHD and cognitive dysfunction is called into question, often because the lead-levels reflect a much higher exposure than what is often faced by the general population, a relatively large study done recently indicates that even moderately high blood lead levels show a strong correlation with ADHD. This suggests either one of two things:

• Other unknown or "hidden" factors were present in the lead-based studies which were the major contributors to impaired mental function and disorders such as ADHD. Even with lower lead levels, these under riding factors were still present, and therefore the major contributing causes to the disorder were still present.

OR

• The sensitivity to lead exposure in children is even higher than previously thought.

An important question we should be asking ourselves is "Does lead exposure beyond a certain point trigger specific ADHD symptoms, or is there an increase in ADHD behavior across the board?".

ADHD is often defined by two major components, the hyperactive/impulsive component and the inattentive component. Based on a recent publication by Nigg and coworkers in the February 2008 Journal of Biological Psychiatry, it appears that the hyperactive/impulsive component of ADHD predominates based on exposure to lead.

Interestingly, the children investigated in the study above were of the inattentive subtype or the combined subtype (both inattentive and hyperactive/impulsive) of ADHD. Based on these results, it is my personal opinion that a child who, under other circumstances may otherwise be of the ADHD inattentive subtype, could instead fall into the ADHD Combined Subtype if he/she is exposed to a specific quantity of lead during the prenatal or early childhood stages of development. Furthermore, I propose that, had the individuals in the study have been of the predominantly Hyperactive/Impulsive Subtype of ADHD, the results would have shown that lead exposure beyond a critical thresh hold would have exacerbated the already-negative hyperactive behaviors for this particular subtype.

In addition to the negative effects surrounding the hyperactive elements of ADHD, the study also found a correlation between low-level lead exposure and child IQ's. This, of course, has been a hotly debated topic for years. While other factors may clearly be at work (lead exposure is often higher in areas with lower socioeconomic status, which is also a factor often correlated with lower IQ scores), the results of numerous studies, many of them recent, still support a strong possible connection.

Theoretically, then, by significantly reducing the prenatal or early-developmental exposure to lead, a child may be at least partially shielded from negative symptoms such as a lower IQ and hyperactive behavior. However, for individuals with the predominantly inattentive form of ADHD, these lead-restrictive measures would be less effective in addressing their inattentive behaviors. Therefore, it is my opinion that reducing lead exposure due to prenatal intervention, iron therapy, or, even possibly chelation methods (both of which will be discussed in future posts), would be most effective for treating the Hyperactive/Impulsive and Combined subtypes of ADHD and less effective for the Predominantly Inattentive ADHD Subtype.

While we should be careful not to overplay or overhype the lead/ADHD connection (especially given the fact that overall lead exposure risks have gone down throughout most of the world in recent years due to the uses of unleaded gasoline and lead-based paint, among other things), it is important to recognize that there is still a statistically significant connection between the two, at least according to a number of recent studies. The Nigg paper, mentioned above, found a strong correlation with hyperactive ADHD-like behavior at much lower lead levels (much closer to the average levels found in much of the United States) than those in most previous studies. This information is particularly important to pregnant mothers, since it has been demonstrated that the negative effects of lead, and other heavy metals and toxins are more harmful on developing brains and nervous systems than to mature ones. The protective effects of reducing lead exposure to mitigate the negative symptoms of ADHD, should not, in this blogger's opinion, be overlooked.

In the next post, we will be discussing how treatment or supplementation with iron may be able to offset some of these harmful effects of early lead exposure on ADHD, should they occur.

Increasing Concerta Medication Dosage: Benefits and Risks

In the last post, we introduced the concept of dosage windows for ADHD medications. In other words, we see that the dosage level of an ADHD medication can be of equal importance to the type of medication used. For more info on this topic, please check out the blog site of Dr. Charles Parker called CorePsychBlog. It is extremely well-organized, concise, and easy to follow, in my humble opinion. This is where I was first introduced to the "window" concept of medications, the term which I have borrowed for the last couple of posts.

This post is meant to expound on the dosage principle in the context of on of the more popular ADHD stimulant medications currently on the market, Concerta (slow-release methylphenidate). We will be drawing information from a few key articles, including one from the 2003 Journal of Pediatrics by Mark A. Stein and coworkers. A copy of the original online journal containing a summary of this article can be found here.

If you do not have time to read all of this post, feel free to skip to the last paragraph at the bottom of the page to get the overall message of this blog entry. If you are looking for more detail, I have addressed the key points made in this article in the major points below:

• The drug Concerta releases the active methylphenidate ingredient into the system at slowly increasing levels over roughly a 12-hour period. The overall effect is similar to that of the traditional tri-daily methylphenidate medication.

• The article studied the positive and negative effects of this medication in 5 to 16 year-old children under three different common prescription doses, 18, 36 and 54 milligram doses. These children were of average or above-average IQ, with about 1/3 being diagnosed as Learning Disabled. About two-thirds of the children had never taken any type of stimulant medication for ADHD before the study.

• Noticeable differences were seen between different ADHD subtypes. For the Inattentive subtype, lower levels doses were optimal, while for the Combined subtype (inattention plus impulsive behavior plus hyperactivity), higher amounts were typically optimal. When the effects of co-occuring disorders such as oppositional defiance (ODD) and learning disabilities were factored out to focus in the ADHD itself, the subtype differences were even greater. This underscores the need for proper subtype diagnosis as opposed to just labeling an individual ADHD.

• For the Primarily Inattentive (PI) subtype of ADHD, the inattention difficulties improved most dramatically with the first 18 mg of medication. Beyond this dosage, only slight effects were seen. This is in agreement with another earlier study which analyzed different doses of another form of methylphenidate for treating ADHD. For the accompanying hyperactivity and impulsive behavioral symptoms (which are often present in the inattentive subtype, just not at the same elevated level of the Combined subtype) were most effectively reduced with the first 18 mg of the medication. While the effectiveness of higher doses leveled off, slight but noticeable improvements were also seen as medication dosage was increased from 18 to 36 mg. At 54 mg, however, improvements stopped or even regressed. This suggests that the "sweet spot" for the Inattentive Subtype of ADHD is somewhere around 18 mg (or slightly higher). Note that Concerta is also available in the 27 mg level, a dosage which was not tested in the study.

• In contrast to the Inattentive Subtype, where the greatest gains were seen from 0 to 18 mg of Concerta, for the Combined Subtype of ADHD, the greatest overall boost in effectivness was seen between 36 to 54 mg. Based on the trends of the graphs in the paper, as well as data from other studies, it appears that doses beyond 54 mg may still be of benefit for several individuals with the combined subtype. In other words, treatment of individuals with the Combined ADHD Subtype typically requires at least 18 mg more medication than those of the Inattentive Subtype (see note at end of the post for an important caveat and exception to this).

• Negative side effects of the medication were minimal at low (18 mg) to middle (36 mg) doses. However, beyond 36 mg, these negative side effects became more pronounced.

• Sleep problems (such as insomnia) began at the 36 mg dosage for Concerta, with the most pronounced effects seen in younger and smaller children.

• Noticeable appetite suppression was seen even at low doses (from 0 to 18 mg), especially for younger and smaller children. However, the overall severity of this was limited. However, the percentage of children who experienced "severe" appetite suppression dramatically increased between 36 to 54 mg treatments of Concerta.

• At 36 mg, the presence of or increase in tics (see related post on ADHD and tics) was seen, and a further increase was seen for some children at the 54 mg dosage.

• None of the dosage levels corresponded to blood pressure increases, and only minimal increases in pulse rates were seen. Compare this to another post on the cardiovascular risks of ADHD stimulant medications.

• A much earlier study on the ADHD medication methylphenidate (an earlier non-Concerta form) suggested that while hyperactive behavior continued to improve at higher doses, the ability to perform cognitive tasks decreased at higher levels of medication. While these effects were difficult to duplicate in future studies, it does suggest an upper limit for certain medications in which going above may lead to a reduction in improvement. We have seen similar effects in previous posts (see the "upside down U curve" in point #6 for tyrosine and clozapine treatment for ADHD here as an example).

A caveat and final blogger's note: Based on the conclusions of the study, it appears that going above the 54 mg limit may be beneficial for certain individuals of the Combined Subtype. While the data of the study may support this, it is important to note that the study only lasted 3 weeks. As a result, long-term effects of high doses of medication were unable to be observed. Additionally, we saw in one of the points above that negative side effects began to creep in at the 36-54 mg level. Based on other blog posts with regards to risk factors of certain ADHD medications as well as potential medication side effects, I urge you to err on the side of caution, especially on issues concerning young and small children (who are at much greater risk for developing severe side effects). In the above study, the highest dosage (54 mg of Concerta) was omitted for the smallest study participant as a precautionary measure.

A quick overall summary of this post: It is imperative that we take ADHD subtype seriously. The take-home message of this blog post should be that lower doses of methylphenidate are often optimal individuals with the Inattentive subtype for ADHD, while those of the Hyperactive-Impulsive (not studied in the above journal article) and Combined subtypes of ADHD typically require significantly higher levels of medication.

Using Zinc to Boost Ritalin's Effectiveness

We have seen that combining stimulant and non-stimulant medications for ADHD can be effective, as evidenced in a previous post on how Risperidone boosts ADHD stimulant medication effectiveness. We have also explored how supplementation with the amino acid tyrosine can boost the effectiveness of clozapine. Now we will be examining another non-medication compound, zinc sulfate and its effects on the popular ADHD drug methylphenidate (Ritalin, Concerta).

Most of the information in this post is gleaned from a 2004 article in the journal BMC Psychiatry on Zinc Sulfate and methylphenidate for children with ADHD. Some key points are listed below:

• The study compared children with ADHD of both genders, ages 5-11 who took either: methylphenidate with zinc sulfate (15 mg zinc) to those who took methylphenidate by itself (with a sugar placebo) for 6 weeks. Results on treatment effectiveness were determined based on both parent and teacher ratings for ADHD behaviors, as well as psychiatrist evaluations every 2 weeks.


• Zinc is required for the proper function of over 100 different enzymes in the body and previous research has shown that a deficiency in this important mineral can be associated with ADHD.


• Zinc also helps regulate levels of the important compound melatonin, which plays a significant role in regulating sleep patterns in individuals both with or without ADHD. Melatonin also plays an important role in regulating levels of the brain chemical dopamine, which is a key factor in ADHD.


• All children in the sample were of the combined subtype (one of the 3 major subtypes of ADHD, which includes hyperactivity, impulsive behavior and inattention), and had not received previous ADHD medications.

• The study found that ADHD symptoms decreased following the 6 week period for the methylphenidate group, but an even more pronounced decrease in negative symptoms when the methylphenidate was combined with zinc. These trends were statistically significant in both the parent and teacher rating studies.

• (Blogger's point, not from article): Based on previous studies and blog posts on the ADHD stimulant medication Adderall, we have seen that psychiatrists generally see even greater levels of improvements for ADHD treatments than do parents or teachers. If this trend holds true to this treatment, then it is possible that these positive effects may be under-representations of the real potential of zinc-methylphenidate combination treatment.

• (Blogger's remark, not from article): While this study showed promise, it did not compare zinc-methylphenidate treatment to zinc treatment by itself. In other words, we cannot tell if zinc treatment actually amplifies the effects of the medication or if it simply targets additional symptoms of the disorder. Given the fact that zinc deficiency is common in individuals with ADHD, it may be the case that zinc supplementation, not methylphenidate may be the main effective treatment factor. Look for future posts on zinc supplementation and ADHD.