Author: Prof. Stephen Faraone

It sound like science fiction, but scientists have been testing computerized methods to train the brains of ADHD people with the goal of reducing both ADHD symptoms and cognitive deficits such as difficulties with memory or attention.   Two main approaches have been used: cognitive training and neurofeedback.

Cognitive training methods ask patients to practice tasks aimed at teaching specific skills such as retaining information in memory or inhibiting impulsive responses.  Currently, results from ADHD brain studies suggests that the ADHD brain is not very different from the non-ADHD brain, but that ADHD leads to small differences in the structure, organization and functioning of the brain.  The idea behind cognitive training is that the brain can be reorganized to accomplish tasks through a structured learning process.  Cognitive retraining helps people who have suffered brain damage so was logical to think it might help the types of brain differences seen in ADHD people.  Several software packages have been created to deliver cognitive training sessions to ADHD people.  You can read more about these methods here: Sonuga-Barke, E., D. Brandeis, et al. (2014). “Computer-based cognitive training for ADHD: a review of current evidence.” Child Adolesc Psychiatr Clin N Am 23(4): 807-824.

Neurofeedback was applied to ADHD after it had been observed, in many studies, that people with ADHD have unusual brain waves as measured by the electroencephalogram (EEG).  We believe that these unusual brain waves are caused by the different way that the ADHD brain processes information.  Because these differences lead to problems with memory, attention, inhibiting responses and other areas of cognition and behavior, it was believed that normalizing the brain waves might reduce ADHD symptoms.  In a neurofeedback session, patients sit with a computer that reads their brain waves via wires connected to their head.  The patient is asked to do a task on the computer that is known to produce a specific type of brain wave.   The computer gives feedback via sound or a visual on the computer screen that tells the patient how ‘normal’ their brain waves are.  By modifying their behavior, patients learn to change their brain waves.  The method is called neurofeedback because it gives patients direct feedback about how their brains are processing information.

Both cognitive training and neurofeedback have been extensively studied.  If you’ve been reading my blogs about ADHD, you know that I play by the rules of evidenced based medicine.  My view is that the only way to be sure that a treatment  ‘works’ is to see what researchers have published in scientific journals.   The highest level of evidence is a meta-analysis of randomized controlled clinical trials.   For my lay readers, that means that that many rigorous studies have been conducted and summarized with a sophisticated mathematical method.   Although both cognitive training and neurofeedback are rational methods based on good science, meta-analyses suggest that they are not helpful for reducing ADHD symptoms.  They may be helpful for specific problems such as problems with memory, but more work is needed to be certain if that is true.

The future may bring better news about these methods if they are modified and become more effective.  You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. & Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.

When my colleagues and I wrote our “Primer” about ADHD, http://rdcu.be/gYyV, the topic of brain mechanisms was a top priority.   Because so much has been written about the ADHD brain, it is difficult to summarize.   Yet we did it with the eight pictures reproduce here in one Figure.   A quick overview of this Figure shows you the complexity of ADHD’s pathophysiology.  There is no single brain region or neural circuit that is affected.   Figures (a) and (b) show you the main regions implicated by structural and functional neuroimaging studies.  As (c) shows, these regions are united by neural networks rich in noradrenalin (aka, norepinephrine) and dopamine, two neurotransmitters whose activity is regulated by medications that treat ADHD.  Figure (d) describes two functional networks.   The Executive Control network is, perhaps, the best described network in ADHD.  This network regulates behavior by linking dorsal striatum with the dorsolateral prefrontal cortex.  This network is essential for inhibitory control, self-regulation, working memory and attention.  The Corticocerebellar network is a well-known regulator of complex motor skills.  Data also suggest it play a role in the regulation of cognitive functions.   Figure (d) describes the Reward Networks of the brain that link ventral striatum with prefrontal cortex.   This network regulates how we experience and value rewards and punishments.   In addition to its involvement in ADHD, this network has also been implicated in substance use disorders, for which ADHD persons are at high risk. Figures (f) (g) and (h) complete the puzzle with additional regions implicated in ADHD whose role is less well understood.  One role for these regions is in the regulation of the Default Mode Network, which controls what the brain does when it is not focused on any specific task (e.g., daydreaming, mind wandering).  People differ in the degree to which they shift between the default mode network and networks like Reward or Executive Control, which are active when we engage the world.  Recent data suggest that the brains of ADHD people may be in ‘default mode’ when they ought to be engaged in the world.

REFERENCE

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

A relatively new area of ADHD research has been examining the association between ADHD and eating disorders (i.e., anorexia nervosa, bulimia nervosa and binge eating disorder).   Nazar and colleagues conducted a systematic review and meta-analysis of extant studies.   They found only twelve studies that assessed the presence of eating disorders among people with ADHD and five that examined the prevalence of ADHD among patients with eating disorders.  Although there were few studies, the total number of people studied was large, 4,013 ADHD cases and 29,404 controls for the first set of studies and 1,044 eating disorder cases and 11,292 controls for the second set of studies.   The meta-analyses of these data found that ADHD people had a 3.8 fold increased risk for and eating disorder compared with non-ADHD controls.   The level of risk was similar for each of the eating disorders.   Consistent with this, their second meta-analysis found that people with eating disorders had a 2.6 fold increased risk for ADHD compared with controls who did not have an eating disorder.  The risk for ADHD was highest for those with binge eating disorder (5.8 fold increased risk compared with controls).   This bi-directional association between ADHD and eating disorders provides converging evidence that this association is real and, given its magnitude, clinically significant.   The results were similar for males and females and for pediatric and adult populations.   We cannot tell from these data why ADHD is associated with eating disorders.  Nazar et al. note that other work implicates both impulsivity and inattention in promoting bulimic symptoms whereas inattention and hyperactivity are associated with craving.  The association may also be due to the neurocognitive deficits of ADHD, which could lead to a distorted sense of self awareness and body image.   Given that ADHD is also associated with obesity, it is possible that some obese ADHD patients have an underlying eating disorder, such as binge eating, which has been associated to obesity in prospective studies.    Also, lisdexamphetamine is FDA approved for treating both binge eating and ADHD, which suggests the possibility that the two conditions share an underlying etiology involving the dopamine system.   We do not know if treating ADHD would reduce the risk for eating disorders as that hypothesis has not yet been tested.  But such an effect would seem likely if ADHD behaviors mediate the association between the two disorders.

REFERENCE

Nazar, B. P., Bernardes, C., Peachey, G., Sergeant, J., Mattos, P. & Treasure, J. (2016). The risk of eating disorders comorbid with attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Int J Eat Disord 49, 1045-1057.

If we are to read what we believe on the Internet, dieting can cure many of the ills faced by humans.  Much of what is written is true. Changes in dieting can be good for heart disease, diabetes, high blood pressure and kidney stones to name just a few examples. But what about ADHD?  Food elimination diets have been extensively studied for their ability to treat ADHD.  They are based on the very reasonable idea that allergies or toxic reactions to foods can have effects on the brain and could lead to ADHD symptoms.

Although the idea is reasonable, it is not such an easy task to figure out what foods might cause allergic reactions that could lead to ADHD symptoms.   Some proponents of elimination diets have proposed eliminating a single food, others include multiple foods and some go as far to allow only a few foods to be eaten so as to avoid all potential allergies.  Most readers will wonder if such restrictive diets, even if they did work, are feasible.  That is certainly a concern for very restrictive diets.

Perhaps the most well-known ADHD diet is the Feingold diet (named after its creator).  This diet eliminates artificial food colorings and preservatives that have become so common in the western diet.   Some have claimed that the increasing use of colorings and preservatives explains why the prevalence of ADHD is greater in Western countries and has been increasing over time.   But those people have it wrong.  The prevalence of ADHD is similar around the world and has not been increasing over time.   That has been well documented but details must wait for another blog.

The Feingold and other elimination diets have been studied by meta-analysis.  This means that someone analyzed several well controlled trials published by other people.  Passing the test of meta-analysis is the strongest test of any treatment effect.    When this test is applied to the best studies available, there is evidence that exclusion of fool colorings helps reduce ADHD symptoms.  But more restrictive diets are not effective.  So removing artificial food colors seems like a good idea that will help reduce ADHD symptoms.   But although such diets ‘work’, they don’t work very well.  On a scale of one to 10 where 10 is the best effect, drug therapy scores 9 to 10 but eliminating food colorings scores only 3 or 4.   Some patients or parents of patients might want to this diet change first in the hopes that it will work well for them.  That is a possibility, but if that is your choice, you should not delay the more effective drug treatments for too long in the likely event that eliminating food colorings is not sufficient.  You can learn more about elimination diets from: Nigg, J. T. and K. Holton (2014). “Restriction and elimination diets in ADHD treatment.” Child Adolesc Psychiatr Clin N Am 23(4): 937-953.

Keep in mind that the treatment guidelines from professional organization point to ADHD drugs as the first line treatment for ADHD.  The only exception is for preschool children where medication is only the first line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available.  You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. & Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.

Although some people view the impulsivity and inattentiveness of ADHD adults as a normal trait, these symptoms have adverse consequences, which is why doctors consider ADHD to be a disorder. The list of adverse consequences is long and now we can add another: broken bones.   A recent study by Komurcu and colleagues examined 40 patients who were seen by doctors because of broken bones and forty people who had not broken a bone.  After measuring ADHD symptoms in these patients, the study found that the patients with broken bones were more impulsive and inattentive than those without broken bones.  These data suggest that, compared with others, adults with ADHD symptoms put themselves in situations that lead to broken bones.  What could those situations be?  Well, we know for starters that ADHD adults are more likely to have traffic accidents.   They are also more likely to get into fights due to their impulsivity.   As a general observation, it makes sense that people who are inattentive are more likely to have accidents that lead to injuriers.  When we don’t pay attention, we can put ourselves in dangerous situations.  Who should care about these results?  ADHD patients need to know about this so that they understand the potential consequences of their disorder.  They are exposed to so much media attention to the dangers of drug treatment that it can be easy to forget that non-treatment also has consequences.  Cognitive behavior therapy is also useful for helping patients learn how to avoid situations that might lead to accidents and broken bones.    This study also has an important message for administrators how make decisions about subsidizing or reimbursing treatment for ADHD.  They need to know that treating ADHD can prevent outcomes that are costly to the healthcare system, such as broken bones.   For example, in a study of children and adolescents, Leibson and colleagues showed that healthcare costs for ADHD patients were twice the cost for other youth, partly due to more hospitalizations and more emergency room visits.  Do these data mean that every ADHD patient is doomed to a life of injury and hospital visits?   Certainly not.  But they do mean that patients and their loved ones need to be cautious and need to seek treatments that can limit the possibility of accidents and injury.

REFERENCES

Komurcu, E., Bilgic, A. & Herguner, S. (2014). Relationship between extremity fractures and attention-deficit/hyperactivity disorder symptomatology in adults. Int J Psychiatry Med 47, 55-63.

Leibson, C. L., S. K. Katusic, et al. (2001). “Use and Costs of Medical Care for Children and Adolescents With and Without Attention-Deficit/Hyperactivity Disorder.” Journal of the American Medical Association 285(1): 60-66.

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD.   Given that acetaminophen is used in many over-the-counter pain killers, correctly reporting such information is crucial.  As usual, rather than relying on one study, looking at the big picture using all available studies is best.  Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677) reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37.  The risk was dose-dependent in the sense that it increased with increased maternal use of acetaminophen.  Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation and infection).  Similar results were reported by another group (http://www.ncbi.nlm.nih.gov/pubmed/25251831), which also showed that risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics.  But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11.  In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life.  The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers.

We can draw a few conclusions from these studies.  There does seem to be a weak, yet real, association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child.  The association is weak in several ways: there are not many studies, they are all naturalistic and the risk ratios are small.   So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen use caused their child’s ADHD.  On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician.  As with many medical decisions, one must balance competing risks to make an informed decision.

Find more evidenced-based blogs at www.adhdinaduls.com.

If we are to read what we believe on the Internet, dieting can cure many of the ills faced by humans.  Much of what is written is true. Changes in dieting can be good for heart disease, diabetes, high blood pressure and kidney stones to name just a few examples. But what about ADHD?  Food elimination diets have been extensively studied for their ability to treat ADHD.  They are based on the very reasonable idea that allergies or toxic reactions to foods can have effects on the brain and could lead to ADHD symptoms.

Although the idea is reasonable, it is not such an easy task to figure out what foods might cause allergic reactions that could lead to ADHD symptoms.   Some proponents of elimination diets have proposed eliminating a single food, others include multiple foods and some go as far to allow only a few foods to be eaten so as to avoid all potential allergies.  Most readers will wonder if such restrictive diets, even if they did work, are feasible.  That is certainly a concern for very restrictive diets.

Perhaps the most well-known ADHD diet is the Feingold diet (named after its creator).  This diet eliminates artificial food colorings and preservatives that have become so common in the western diet.   Some have claimed that the increasing use of colorings and preservatives explains why the prevalence of ADHD is greater in Western countries and has been increasing over time.   But those people have it wrong.  The prevalence of ADHD is similar around the world and has not been increasing over time.   That has been well documented but details must wait for another blog.

The Feingold and other elimination diets have been studied by meta-analysis.  This means that someone analyzed several well controlled trials published by other people.  Passing the test of meta-analysis is the strongest test of any treatment effect.    When this test is applied to the best studies available, there is evidence that exclusion of fool colorings helps reduce ADHD symptoms.  But more restrictive diets are not effective.  So removing artificial food colors seems like a good idea that will help reduce ADHD symptoms.   But although such diets ‘work’, they don’t work very well.  On a scale of one to 10 where 10 is the best effect, drug therapy scores 9 to 10 but eliminating food colorings scores only 3 or 4.   Some patients or parents of patients might want to this diet change first in the hopes that it will work well for them.  That is a possibility, but if that is your choice, you should not delay the more effective drug treatments for too long in the likely event that eliminating food colorings is not sufficient.  You can learn more about elimination diets from: Nigg, J. T. and K. Holton (2014). “Restriction and elimination diets in ADHD treatment.” Child Adolesc Psychiatr Clin N Am 23(4): 937-953.

Keep in mind that the treatment guidelines from professional organization point to ADHD drugs as the first line treatment for ADHD.  The only exception is for preschool children where medication is only the first line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available.  You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. & Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.

Although some people view the impulsivity and inattentiveness of ADHD adults as a normal trait, these symptoms have adverse consequences, which is why doctors consider ADHD to be a disorder. The list of adverse consequences is long and now we can add another: broken bones.   A recent study by Komurcu and colleagues examined 40 patients who were seen by doctors because of broken bones and forty people who had not broken a bone.  After measuring ADHD symptoms in these patients, the study found that the patients with broken bones were more impulsive and inattentive than those without broken bones.  These data suggest that, compared with others, adults with ADHD symptoms put themselves in situations that lead to broken bones.  What could those situations be?  Well, we know for starters that ADHD adults are more likely to have traffic accidents.   They are also more likely to get into fights due to their impulsivity.   As a general observation, it makes sense that people who are inattentive are more likely to have accidents that lead to injuriers.  When we don’t pay attention, we can put ourselves in dangerous situations.  Who should care about these results?  ADHD patients need to know about this so that they understand the potential consequences of their disorder.  They are exposed to so much media attention to the dangers of drug treatment that it can be easy to forget that non-treatment also has consequences.  Cognitive behavior therapy is also useful for helping patients learn how to avoid situations that might lead to accidents and broken bones.    This study also has an important message for administrators how make decisions about subsidizing or reimbursing treatment for ADHD.  They need to know that treating ADHD can prevent outcomes that are costly to the healthcare system, such as broken bones.   For example, in a study of children and adolescents, Leibson and colleagues showed that healthcare costs for ADHD patients were twice the cost for other youth, partly due to more hospitalizations and more emergency room visits.  Do these data mean that every ADHD patient is doomed to a life of injury and hospital visits?   Certainly not.  But they do mean that patients and their loved ones need to be cautious and need to seek treatments that can limit the possibility of accidents and injury.

REFERENCES

Komurcu, E., Bilgic, A. & Herguner, S. (2014). Relationship between extremity fractures and attention-deficit/hyperactivity disorder symptomatology in adults. Int J Psychiatry Med 47, 55-63.

Leibson, C. L., S. K. Katusic, et al. (2001). “Use and Costs of Medical Care for Children and Adolescents With and Without Attention-Deficit/Hyperactivity Disorder.” Journal of the American Medical Association 285(1): 60-66.