The study was conducted by a team of researchers at the University of Cincinnati and published in Archives of Pediatrics. The researchers examined the results of the “ADHD Collaborative” — a initiative in the greater Cincinnati region aimed to improve the adherence of ADHD treatment guidelines by local community pediatricians. The study included 785 children between 7-11 years of age treated by 158 community physicians from 47 separate practices in greater Cincinnati. The children were evaluated when they first started treatment and 3, 6, 9, and 12 months later. The researchers were interested in examining the effectiveness of the treatment in reducing ADHD symptoms and reducing functional impairment (i.e., how the children did at school, home, and with their peers).

The initial results were very promising.

As you can see above, the treatment resulted in a rapid and dramatic decrease in ADHD symptoms as reported by both parents and teacher. This is consistent with most research on the effectiveness of ADHD medications: they are very effective in reducing ADHD symptoms.

On first impression, the picture became less rosy, or better said, outright gloomy, when the authors examined the effects of the treatment on functional impairment. See for example the effect of the treatment on academic difficulties in reading, math, writing, and overall school performance:

The number of children experiencing impairment in reading, math, writing, and overall in school remained virtually identical during the entire year of the study. This suggests that the intervention did not have much of an impact on the kids’ school functioning. The same pattern of results was observed for the kids’ peer, sibling, and family relations.

Does this mean that medication for ADHD is simply ineffective? Not really. What it means is that medication alone may not have a significant impact on the child’s functional domains.  It is possible that medication provides the foundation for additional interventions to work. However, there is a more relevant limitation of this study. If you compare the two graphs above, you will see that the Y axis of the first graph refers to symptoms of ADHD. In contrast, the Y axis of the second graph refers to the % of children showing impairment in those categories. Why is this significant? Because the first graph allows us to observe changes in a continuous scale of symptoms (we would see even a small change in symptoms). However, the graph below does not allow us to see the effect of the medication on the LEVEL of impairment of the children. That is, we only see that the percentage of children who show impairment did not change, but it is still possible that these children improved significantly!- albeit still performing in the impaired range. So although it is disappointing that the treatment alone did not result in a reduction of the percentage of children who had functional impairment, the picture may not be a gloomy as we think.

The reference:
Epstein, J., Langberg, J., Lichtenstein, P., Altaye, M., Brinkman, W., House, K., & Stark, L. (2010). Attention-Deficit/Hyperactivity Disorder Outcomes for Children Treated in Community-Based Pediatric Settings Archives of Pediatrics and Adolescent Medicine, 164 (2), 160-165 DOI: 10.1001/archpediatrics.2009.263

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The Results:

1. 8.7% of the entire sample met diagnostic criteria for ADHD. That is, the rate of ADHD, as diagnosed by a structure diagnostic clinical interview, was close to 10% of US teens.

2. While controlling for all other variables, prenatal exposure to tobacco increased the risk of having ADHD by 140%.

3. While controlling for all other variables, current lead levels also increased the risk for having ADHD and this effect was ‘linear’ in relation to lead levels. Specifically, having lead levels in the second tertile (0.09 – 1.2 ug/dl ) increased the risk by 70%. Having lead levels in the third tertile (>1.3 ug/dl) increased the risk by 130%.

4. Other variables associated with an increased risk included: being a boy, being non-Hispanic white, and having attended preschool.

5. The combination of prenatal tobacco exposure and having high lead levels increased the risk for ADHD by 700%.

This study is very compelling given the number of potential explanatory variables that were included in the analysis. The results strongly point towards an association between tobacco exposure before birth and ADHD risk. However, one important explanatory variable was omitted: parental history of ADHD. We know that there is a strong familial risk for ADHD, in that children of parents who have ADHD are a significantly higher risk of having ADHD themselves. It is then possible that those ADHD mothers are more likely to smoke during pregnancy, and that it is the maternal history of ADHD and not the tobacco exposure that explains some of these results. The authors correctly noted this issue but argued that other studies have were able to control for maternal history of ADHD have obtained similar results, making this alternative explanation unlikely.

The reference:
Froehlich, T., Lanphear, B., Auinger, P., Hornung, R., Epstein, J., Braun, J., & Kahn, R. (2009). Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder PEDIATRICS, 124 (6) DOI: 10.1542/peds.2009-0738

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The authors of the Journal of Child Psychology and Psychiatry study examined participants from two independent longitudinal studies of ADHD. The first study started in the 1980s and included 140 6-to-17 year-old boys with ADHD, 206 siblings, 280 parents, and 120 non-ADHD peers. These kids were assessed for up to 10 years after the initiation of the study. The second study started in 1993 and included 140 6-to-17 year-old girls, 183 siblings, 274 parents, and 122 non-ADHD peers. These girls were followed for up to 5 years. The final sample for the study included 143 ADHD girls and 147 ADHD boys. Both groups were on average approximately 11 years old at the time of the first assessment. However boys were significantly older (mean age 19) at the time of the last followup compared to the girls (mean age 16).

The ADHD diagnoses were obtained via a 3-step procedure that included a comprehensive psychiatric interview. This greatly limits the possibility that some of the ADHD cases included in the study were misdiagnoses. An similar assessment of ADHD symptoms and co-morbid conditions were conducted during the follow up period.

The Results:

1. As you can see from the graphic below, the authors found that ADHD symptoms decline with age in a non-linear fashion. Specifically, the decline in symptoms accelerates with age.

2. As also noted in the graphic below, girls had significantly more ADHD symptoms than boys across all developmental periods. While in the graphic it looks like this difference was more pronounced during early childhood, the statistical analysis conducted indicated that the sex difference in ADHD symptoms was consistent (the same) at all ages.

Developmental course of ADHD

3. The authors also found a sex difference in the developmental progression of co-morbid conditions. Specifically, while in childhood ADHD in boys and girls were associated with the same co-morbid conditions (Mood Disorders, Disruptive Behavior Disorders, and Anxiety), during adolescence ADHD was no longer associated with anxiety for boys. In contrast, girls continued to show high co-morbidity between ADHD and anxiety in adolescence.

Psychiatric Co-morbidity of ADHD

The good news is that ADHD symptoms appear to decrease with age, and that this decline accelerates as children get older. However, the news are not as good for girls. The study shows that symptoms in girls appear to be more severe than in boys, and that for girls there are more co-morbid conditions during adolescence than for boys. While this may suggest that ADHD is more severe in girls than in boys, we should keep in mind that the results of any study is highly dependent on the sample used, and more importantly the way participants were recruited. For example, boys and girls in this study came from two independent samples, and unknown methodological differences between these samples could be driving some of the results. In addition all of the participants with ADHD were initially included after getting a clinical diagnosis for ADHD by a referral source, which was later confirmed by the study’s own clinician (details on how the recruitment took place were not provided). Therefore, it is possible that these findings reflect sex differences in the initial clinical identification of ADHD by the kid’s clinicians. Specifically, it is possible that girls who were diagnosed and subsequently entered the study simply did so because of experiencing more severe symptoms. While indeed there are some methodological limitations, this is one of the only studies who have provided comprehensive empirical data that help us understand the differences between boys and girls in the progression of ADHD symptoms and co-morbid conditions during childhood and adolescence.

The reference: Monuteaux, M., Mick, E., Faraone, S., & Biederman, J. (2009). The influence of sex on the course and psychiatric correlates of ADHD from childhood to adolescence: A longitudinal study Journal of Child Psychology and Psychiatry DOI: 10.1111/j.1469-7610.2009.02152.x

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1. In this new study the author first presented 4 issues that remain unresolved from previous research linking maternal obesity and ADHD
2. Since obesity is associated with distress, is it possible that it is the distress during pregnancy that increases the risk for ADHD rather than the obesity?
3. It is possible that maternal obesity and child ADHD are simply related to a common genetic factor. In such a case, it would be the genetic factor, and not the obesity that increases the risk for ADHD
4. Maternal obesity is associated with small birth weight due to fetal growth restrictions, and some studies have linked small birth size to ADHD, possibly through its effects on emotional regulation. Thus, is small birth size the possible link between maternal obesity and ADHD?
5. Maternal obesity is also associated with childhood obesity. Is it possible then than the increased risk for ADHD is due to childhood obesity?

To begin to tackle these issues, the author examined a cohort of women who were pregnant in Sweden from 1999 to 2000. The cohort for this analysis included 1,714 mother-child dyads who were evaluated when the child was 5 years of age. The Body Mass Index of the mothers was obtained during pregnancy and divided into 4 groups: underweight (15–19.99), normal weight (20–24.99),  overweight (25–29.99), and obese (+30). ADHD symptoms and emotionality  at age 5 were assessed via a questionnaires completed by both mothers and teachers. A number of covariates (or potentially explanatory factors) were also measured including maternal stress during pregnancy (divorce, financial problems, etc), socio-economic   status, smoking, the child’s own weight, and depression.

The results:

1. 37% of the mothers were classified as either overweight or obese (28% overweight and 10% obese)
2. Obese mothers were significantly more depressed than the mothers in any of the other weight categories
3. Children of obese mothers had significantly more symptoms of inattention but not hyperactivity when these symptoms were reported by the teachers. Specifically, maternal obesity was associated with a 2-fold increase in risk of teacher-rated inattention symptoms when compared to the children of normal-weight mothers. This association remained stable after controlling for the possible explanatory factors.
4. Maternal Obesity was also associated with an increased risk for negative emotion regulation difficulties as indicated by a teacher-reported emotionality questionnaire.
5. Maternal Obesity was not associated with any symptom when the symptoms were reported by the mother.

A couple of things were surprising. First, the results of the teacher-reported inattention problems were strong, which was of note given that no association was found between obesity and hyperactivity. This discrepancy between inattention and hyperactivity actually points towards a clear link between obesity and adhd (at least inattentive type). That is, since obesity was associated with inattention but not hyperactivity, it is unlikely that the original findings reflected simply an association between obesity and more general behavioral problems in childhood. Instead, the link seems to be specific to one aspect of ADHD. Second, the lack of association between obesity and maternal reported symptoms continues a pattern of findings I have previously discussed (see  for example this article on the effects of multiple daycare arrangements) that suggests that there are some limitations in the nature of maternal reports of the child behavior. In my experience working on several large scale family-based longitudinal studies, fathers and teachers reports of kids’ behaviors tend to agree with each other, but these reports do not always agree with the mother’s. It seems that mothers often see, or report, different behavioral tendencies in their children when compared to what teachers see (or report).

In sum, the study provides additional evidence linking maternal obesity to inattention problems in early childhood. This study expands previous findings by also showing that such a link can not be fully explained by a number of potential factors, such as maternal stress, depression, and socio-economic status. However, please also note that this study did not actually assessed for the presence of ADHD. That is, these kids did not undergo the comprehensive evaluation needed for an accurate diagnosis of ADHD. Instead, the study assessed ADHD-related symptoms as reported by teachers and parents. It would be interesting to see if obesity is associated with true ADHD diagnoses in this population.

The reference: Rodriguez, A. (2009). Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children Journal of Child Psychology and Psychiatry DOI: 10.1111/j.1469-7610.2009.02133.x

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In the latest issue of Pediatrics, a team led by Dr. Joseph Biederman from Harvard Medical School published an examination of the association between ADHD medication and future psychiatric conditions. For this study, the researchers followed 112 children age 6 to 17 for approximately 10 years. All of these children had a diagnosis of ADHD. 73% of these children had a life time use of stimulant medication and 27% had never used the medication. The authors compared the probability of having a co-morbid psychiatric disorder 10 years after the start of the study among kids who had used medication against those who never used medication.

The results:

1. Those taking the medication were significantly LESS likely to develop Major Depression than those who were medication free. Specifically the life time risk (up to age 21) for major depression among kids with ADHD who never took medication was 69%, compared to only 24% for those who took medication.
2. Medication users were less likely to develop Conduct Disorder when compared to medication free kids. Specifically, the risk to develop Conduct Disorder for those who never took medication was 67%, compared to only 22% for those who took medication.
3. Similar effects were observed for Anxiety (no medication users risk 60% vs. 7% for medication users), Oppositional Defiant Disorder (no medication users risk 88% vs. 40% for medication users).
4. Children who took ADHD medication were also less likely to repeat a grade (26% risk) when compared to those who never took ADHD meds (63% risk)
5. ADHD medication did not have a statistical significant impact on the risk of developing bipolar disorder.

This study is very compelling and it is unique because of the very long follow up period (10 years). This provides credible evidence of the potential long-term effects (and in this case benefits) of medication use. I was surprised at the consistency of the findings for multiple psychiatric disorders. Honestly, I was expecting to see the opposite results, mostly because medication is now commonly used among the most severe cases. Therefore, long term examinations of outcome could show more detrimental outcomes among those who use medications, but not because of the medication, but because these children have more severe disorders than those who are not prescribed the medication. But the results of the study show that even in the face of this possible confound, the beneficial effects of these medications overrode the effects of having more severe ADHD at the initiation of the study. However, there is no indication that this was the case in this particular study. That is, although those who took the medication were significantly younger than medication-free kids at the start of the study (possibly suggesting a more severe type of ADHD), it is unclear whether these kids had more severe ADHD at baseline. Yet again, if this had been the case, then the results are even more striking because they indicate that when compared to ‘no medication’, medication use results in a greater reduction of the risk of future psychopathology, even when the kids that take the medication have a more severe form of ADHD.

Unfortunately, Dr. Biderman has recently been the source of some controversy because of his involvement as a consultant for some pharmacology companies. This is likely going to be used by critics of medication use to discredit these findings. However, from a purely scientific perspective, the results are compelling and the science strong. Despite the relatively small sample size and other minor methodological limitations (diagnoses were based on DSM-III criteria), it is rare to see such a longitudinal study expanding 10 years that included complete psychiatric evaluations during the follow up periods.

Disclaimer: I have never worked as a consultant for any Pharmaceutical company.

Biederman, J., Monuteaux, M., Spencer, T., Wilens, T., & Faraone, S. (2009). Do Stimulants Protect Against Psychiatric Disorders in Youth With ADHD? A 10-Year Follow-up Study PEDIATRICS, 124 (1), 71-78 DOI: 10.1542/peds.2008-3347

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Surprisingly, there is a lack of longitudinal long term research exploring the effectiveness of ADHD medication across multiple grades. Instead, most ADHD research examining academic outcomes are relatively short (within one year) or have very small sample sizes. However, in the latest issue of the Journal of the American Academy of Pediatrics, Dr. Richard Scheffler and a team from the University of California at Berkeley, reported the findings of a comprehensive long term examination of the effectiveness of ADHD medications on academic achievement.

The authors examined a representative population cohort of children entering Kindergarten in the late 1990′s. The study cohort included 11,890 children who entered Kindergarten in 1998. These children were examined yearly until the end of their 5th grade. The authors gathered information on whether the child had an ADHD diagnosis, whether the child was taking medication (more of this below), and the mathematics and reading achievement levels of all the kids during the 5 year study.

The estimation of the medication use was a bit tricky. During 5th grade, the families were asked whether the child was taking medication for ADHD at that time. If the child was not taking medication, the authors assumed that the child had not taken ADHD medication during the duration of the study. If the child was taking a medication in 5th grade, the parents were then asked to report the length of medication use, which was used to estimate past years’ use.

The authors then compared children who had been medicated to those with a diagnosis of ADHD but who had not received any medications.

The Results:

1. 9% of the sample had a life-time diagnosis of ADHD by 5th grade. This does not mean that 9% of 5th graders had ADHD. It means that by 5th grade, 9% of those who entered kindergarten in 1998 had received an ADHD diagnosis sometime during their lives.
2. 68 % of kids with ADHD had taken medication for their condition.
3. While controlling for a number of individual and family characteristics, medicated ADHD kids had significantly higher mathematics achievement scores across the different grades than the non-medicated ADHD kids. Although this difference is statistically significant, the authors reported that the gains represent the average gain expected during 0.19 school year over a 6 year period.
4. There was no difference between those medicated at a single year vs. those medicated at multiple years in their mathematics achievement scores.
5. Children who were medicated in multiple years had significantly higher reading achievement scores than the non-medicated ADHD peers. This reflects gains of 0.29 school years over 6 years.

Despite the limitations of this study regarding how medication use was estimated (retrospectively via parental report, no information on dosage, gaps in administration, etc), there is one very compelling overall finding: If we are to assume that severity of ADHD is associated with the likelihood of medication use (the more severe the more likely you are to be medicated), these findings show that medications are effective in improving academic achievement even among these ‘severe’ kids. But we can’t test that hypothesis because the study did not include data about the initial severity of ADHD prior to medication use. Someone could also argue that the effects observed were not due to the medication, but instead to other untapped family characteristic that differentiated those who tried medications vs. those who did not. That is, it is possible that factors that make a family more likely to try medication for their ADHD kids contribute to the kids better long-term academic performance.
The reference: Scheffler, R., Brown, T., Fulton, B., Hinshaw, S., Levine, P., & Stone, S. (2009). Positive Association Between Attention-Deficit/ Hyperactivity Disorder Medication Use and Academic Achievement During Elementary School PEDIATRICS, 123 (5), 1273-1279 DOI: 10.1542/peds.2008-1597

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Research studies on the neurocognitive profiles (memory, attention, executive functioning, etc) of kids with attention-deficit-hyperactivity disorder have one common denominator: there is no unified or common neuropsychological profile that characterizes ADHD. That is, there is no specific pattern of memory, language, attention, etc., deficits that are universally common in kids of ADHD. Such diverse neuropsychological profile reflects the heterogeneity and diversity of ADHD itself. However, there is one finding that is consistently observed in most studies. When compared to non-affected kids, those with ADHD have significantly variable or uneven performance across most tasks. This is noticeable on cognitive tasks that require sustained periods of attention. On these tasks, children with ADHD show marked within-task variability, oscillating between normative and impaired performance. Thus, instead of consistent impaired attention, most kids with ADHD show variable attention, or rapid “lapses” in attention.

Yet, despite the popularity of stimulant medications in the treatment of ADHD, there has been no single randomized, placebo-controlled study on the effects of methylphenidate on lapses of attention. The last issue of the Journal of Abnormal Child Psychology published a very sound study on the effects of methylphenidate on attention problems.

The study was conducted at the University at Buffalo (SUNY) and included 49 children with a diagnosis of ADHD. The sample included 39 boys and 10 girls, age 9 to 12, of average IQ, and average academic achievement. Twenty nine were diagnosed with ADHD-combined type, 8 were diagnosed with ADHD-inattentive type, and 2 were diagnosed with ADHD-hyperactive/impulsive type. All kids were not taking medication at the start of the trials. Specifically, those kids who were taking stimulant medication were asked to stop at least 24 hours prior to the first day, and those who were taking Strattera were asked to stop the medication at least 7 days before the first day (because Strattera takes longer to clear from the body). These kids were randomly assigned to a medication or a placebo condition. The medication consisted of long active Concerta provided at dosages ranging from .3 to .6 mg/kg.

During the testing, the children completed a simple computerized test of attention called the X and O Discrimination Task, which is very sensitive to lapses in attention. Specifically, the kids were presented with either the letter X or the letter O, and they had to respond by pressing two different corresponding keys as fast as possible. The task included 10 practice trials and 100 task trials.

To measure variability the authors focused on the right tail of reaction time distribution. When a child is presented with the X or O the computer records how long it takes the child to respond (in milliseconds). Since ADHD is characterized by variability in attention, the interest in the responses to the X or O task was not really on how how fast the child responded, but instead on how variable the child responded. For example, a child with little variability in responses would look like this:

Note that on the horizontal axis you can see the milliseconds and on the vertical axis you can see the number of times the child responded at each speed. In this example, the child responded 50 times at 500ms, 40 times at 600ms, and 10 times at 700ms. This could be considered a highly stable pattern of performance in that most of the responses were between 500 and 700ms. Now compare that performance to a performance like this:

In this case the responses are still highly stable (all responses within 300ms of each other) but the responses were slower. So this is what you would see if the child was simply slow in responding. Now, compare the two previous graphs to the pattern of responses below:
In this final case, the child was not necessarily slow, but the responses were more variable in that in some trials the child was very fast (in 5 of the trials the child responded within 400ms) while in some trials the child was very slow. Since this type of variability (rather than simple slowness) is commonly observed in ADHD, the authors examined whether Concerta affected the variability in responses during the task.

The results:

1. The authors found a significant effect of the medication on speed, and this effect was dose-dependent. That is, those taking the placebo were significantly slower responding to the task than kids taking a low dose of methylphenidate. Furthermore, kids that were taking a low dose of methylphenidate were significantly slower than those taking a high dose of the medication. Therefore, the results show a strong effect of the medication in increasing speed of responding.

2. The authors also found that the medication resulted in a significant reduction in variability (deviation from the mode), however this was not dependent upon dosage. That is, kids who took the medication showed significantly more consistent/stable responses than kids who took the placebo, but there was no difference in response variability between those taking a low vs. a high dosis of methylphenidate.

3. The increase in speed was not at the cost of accuracy. On the contrary, Kids taking the medication were not only faster and less variable than those taking the placebo, but they were also more accurate.

This study thus provides strong empirical support for the effectiveness of Concerta in facilitating attentional processes. Specifically, methylphenidate seems to 1) improve speed of responding (likely by facilitating sensory-motor processing) and 2) reduce variability in performance (likely by reducing lapses in attention).

Now some final thoughts about this study. This study was conducted by an academic team (university-based) and was financed by the National Institutes of Health (NIH)– NOT by the makers of the drug.
Reference: Spencer, S., Hawk, L., Richards, J., Shiels, K., Pelham, W., & Waxmonsky, J. (2009). Stimulant Treatment Reduces Lapses in Attention among Children with ADHD: The Effects of Methylphenidate on Intra-Individual Response Time Distributions Journal of Abnormal Child Psychology DOI: 10.1007/s10802-009-9316-2

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