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We know from many studies that ADHD is associated with a slightly lower intelligence quotient (IQ) and with problems in thinking known as executive function deficits. If that's the case, you might think that people with a high IQ cannot have ADHD.  You would be wrong. Data on groups sometimes mislead us about individuals. Although on average, ADHD people have IQ scores that are about 9 points lower than others, there is a wide spread of IQs in both ADHD and non-ADHD people. So many people with ADHD have higher IQs than those without ADHD and vice-versa. Moreover, studies of people with high IQs support the idea that ADHD can be validly diagnosed among very intelligent individuals.

A series of studies using Antshel and colleagues showed that the clinical profile of high IQ ADHD was very similar to what has been observed for ADHD in general. For example, like their less intelligent counterparts, high IQ ADHD children have an increased risk for mood, anxiety, and disruptive behavior disorders. Children with a high IQ and ADHD showed a pattern of familial transmission as well as cognitive, psychiatric, and behavioral impairments consistent with the diagnosis of ADHD. The degree to which ADHD persisted into adulthood was also similar between the two groups.

In studies of adults with ADHD, the same group concluded that "adults with ADHD and a high IQ display patterns of functional impairments, familiarity and psychiatric co-morbidities that parallel those found in the average-IQ adult ADHD population." Of particular interest, despite their high intelligence, High-IQ adults with ADHD show impaired executive functioning, and their performance on tests of executive functioning predicted life impairments.

Why are these data important? Milioni and colleagues argue that among higher IQ adults with ADHD, a higher degree of intellectual efficiency may compensate for deficits in executive functions. This ability to compensate allows them to succeed in many tasks, which otherwise might have been impaired by their ADHD symptoms. But, in many cases, such compensation is not sufficient or is too burdensome. When compensation fails, ADHD symptoms and other impairments emerge. When this occurs later in life, some clinicians are reluctant to diagnose ADHD. Caution is warranted, but clinicians need to know that the diagnosis of ADHD among high IQ is valid.

Although ADHD was conceived as a childhood disorder, we now know that many cases persist into adulthood. My colleagues and I charted the progression of ADHD through childhood, adolescence, and adulthood in our "Primer" about ADHD,http://rdcu.be/gYyV.  Although the lifetime course of ADHD varies among adults with the disorder, there are many consistent themes, which we described in the accompanying infographic.  Most cases of ADHD startin uterobefore the child is born. As a fetus, the future ADHD person carries versions of genes that increase the risk for the disorder. At the same time, they are exposed to toxic environments. These genetic and environmental risks change the developing brain, setting the foundation for the future emergence of ADHD.

In preschool, early signs of ADHD are seen in emotional lability, hyperactivity, disinhibited behavior, and speech, language, and coordination problems. The full-blown ADHD syndrome typically occurs in early childhood, but can be delayed until adolescence.  In some cases, the future ADHD person is temporarily protected from the emergence of ADHD due to factors such as high intelligence or especially supportive family and/or school environments. But as the challenges of life increase, this social, emotional, and intellectual scaffolding is no longer sufficient to control the emergence of disabling ADHD symptoms. Throughout childhood and adolescence, the emergence and persistence of the disorder are regulated by additional environmental risk factors such as family chaos along with the age-dependent expression of risk genes that exert different effects at different stages of development. During adolescence, most cases of ADHD persist and by the teenage years, many youths with ADHD have onset with a mood, anxiety, or substance use disorder.  Indeed, parents and clinicians need to monitor ADHD youth for early signs of these disorders. Prompt treatment can prevent years of distress and disability. By adulthood, the number of comorbid conditions has increased, including obesity, which likely has effects on future medical outcomes.

The ADHD adult tends to be very inattentive by showing fewer symptoms of hyperactivity and impulsivity. They remain at risk for substance abuse, low self-esteem, occupational failure, and social disability, especially if they are not treated for the disorder.  Fortunately, there are several classes of medications available to treat ADHD that are safe and effective. And the effects of these medications are enhanced by cognitive behavior therapy, as I've written about in prior blogs.

Suicide is one of the most feared outcomes of any psychiatric condition. Although its association with depression is well known, a small but growing research literature shows that ADHD is also a risk factor for suicidality.  Suicide is difficult to study. Because it is relatively rare, large samples of patients are needed to make definitive statements.
Studies of suicide and ADHD must also consider the possibility that medications might elevate that risk. For example, the FDA placed a black box warning on atomoxetine because that ADHD medication had been shown to increase suicidal risk in youth.  A recent study of 37,936 patients with ADHD now provides much insight into these issues (Chen, Q., Sjolander, A., Runeson, B., D'Onofrio, B. M., Lichtenstein, P. & Larsson, H. (2014). Drug treatment for attention-deficit/hyperactivity disorder and suicidal behavior: a register-based study. BMJ 348, g3769.). In Sweden, such large studies are possible because researchers have computerized medical registers that describe the disorders and treatments of all people in Sweden. Among 37,936 patients with ADHD, 7019 suicide attempts or completed suicides occurred during 150,721 person-years of follow-up. This indicates that, in any given year, the risk for a suicidal event is about 5%. For ADHD patients, the risk for a suicide event is about 30% greater than for non-ADHD patients. Among the ADHD patients who attempted or completed suicide, the risk was increased for those who had also been diagnosed with a mood disorder, conduct disorder, substance abuse, or borderline personality. This is not surprising; the most serious and complicated cases of ADHD are those that have the greatest risk for suicidal events. The effects of the medication were less clear.  The risk for suicide events was greater for ADHD patients who had been treated with non-stimulant medication compared with those who had not been treated with non-stimulant medication. A similar comparison showed no effect of stimulant medications. This first analysis suffers from the fact that the probability of receiving medication increases with the severity of the disorder. To address this problem, the researchers limited the analyses to ADHD patients who had some medication treatment and then compared suicidal risk between periods of medication treatment and periods of no medication treatment. This analysis found no increased risk for suicide from non-stimulant medications and, more importantly, found that for patients treated with stimulants, the risk for suicide was lower when they were taking stimulant medications. This protective effect of stimulant medication provides further evidence of the long-term effects of stimulant medications, which have also been shown to lower the risks for traffic accidents, criminality, smoking, and other substance use disorders.

Over the past few decades, a consensus has emerged among psychopathologists that some patients exhibit a well-defined syndrome referred to as sluggish cognitive tempo or SCT.

There are no diagnostic criteria for SCT because it has not yet been accepted as a separate disorder by the American Psychiatric Association. People with SCT are slow-moving, indolent, and mentally muddled. They often appear to be lost in thoughts, daydreaming, drowsy or listless. In reviewing these symptoms and the literature, Barkley suggested that SCT be referred to as Concentration Deficit Disorder (CDD). This term is less pejorative, but is not yet commonly used.

Becker and colleagues recently evaluated the internal and external validity of SCT via a meta-analysis of 73 studies. Internal validity addresses the consistency of SCT symptoms as a measure of an underlying construct. Based on factor analytic studies using more than 19,000 participants, the authors concluded that the items purported to measure SCT are sufficiently correlated with one another to justify the idea that they measure the same underlying construct.

Further support for internal validity was found in studies reporting high test-retest and interrater reliability. As regards ADHD, the authors found that SCT correlated significantly with both inattentive (r = 0.72) and hyperactive-impulsive (r = 0.46) symptoms in adults. The greater correlation with inattentive symptoms makes sense given the nature of SCT symptoms. So these data confirm two key points about SCT: 1) it is associated with ADHD symptoms, and 2) it is a meaningful construct in its own right. Very little is known about the implications of SCT for the treatment of ADHD.  

In a naturalistic study of 88 children and adolescents with ADHD, Ludwig and colleagues examined the effect of SCT on the response of ADHD symptoms to methylphenidate. They found no significant differences in treatment response between subjects with and without SCT. McBurnett and colleagues tested the effects of atomoxetine on SCT in children with ADHD and dyslexia (ADHD+D) or dyslexia only. Atomoxetine treatment led to significant reductions in both ADHD symptoms and SCT outcomes.

Because controlling for changes in ADHD symptoms did not predict changes in SCT outcomes, the authors concluded that change in SCT in response to atomoxetine is mostly independent of change in ADHD. Although these data are preliminary and in need of replication, they do provide some guidance for clinicians dealing with ADHD patients who also have SCT.

One of the many great contributions of Dr. Russell Barkley was his conceptualization of ADHD as a disorder of self-regulation. ADHD people have difficulties regulating their behavior, which lead to the classic diagnostic criteria of hyperactivity and impulsivity, and they have problem regulating cognitive processes which leads to the well-known inattentive diagnostic criteria for the disorder.    

In a 2010 paper, Dr. Barkley argued persuasively that deficient emotional self-regulation should also be considered a core component of ADHD alongside deficient behavioral and cognitive self-regulation.  Although the DSM 5 did not add any emotional symptoms to the revised criteria for ADHD a new paper by Graziano and Garcia supports Dr. Barkley's position.  

They conducted a meta-analysis of 77 studies of emotional dysregulation that comprised a total of 32,044 participants. They defined emotional dysregulation as the failure to modify emotional states in a manner that promotes adaptive behavior and leads to the success of goal-directed activities. They identified three types of emotional dysregulation: emotion recognition and understanding (ERU), emotional reactivity/negativity/lability (ERNL), and empathy/callous-unemotional traits (ECUT).  

ERU refers to the ability to perceive, process, and infer one's own emotions and the emotions of others.  ERNL refers to the intensity and valence of the emotional response.  Reactivity refers to the rapidity of the emotional response (e.g., is a person quick-tempered rather than reflective); negativity refers to the valence of the emotion.  

Is it extreme or appropriate to the situation; lability refers to how quickly emotional states shift or cycle over time. The ECUT dimension has two poles.  At one extreme is the empathic person, whose reactions are guided by a clear understanding of the emotional states of others.  At the other pole is the psychopath who shows little or no emotion to stimuli that evoke strong emotional reactions in the average person.    

When the data from the 77 studies were sorted into these three categories, the authors found that ADHD people had impairments in all three domains. The magnitude of impairment was a bit greater for ERNL than it was for ECUT and ERU, but not dramatically so.  The association between ADHD and these domains of emotional dysregulation increased with increasing age. It is for this reason that some ADHD experts think that emotional dysregulation should be included in the diagnostic criteria for adult ADHD. Because behavioral hyperactivity diminishes with age, these criteria are less sensitive for adult ADHD than they are for child ADHD. Substituting emotional dysregulation items for hyperactivity items could, potentially, improve diagnoses of adult ADHD.  Future work will address this issue.  In the meanwhile, those who screen and diagnose adult ADHD should be aware that symptoms of emotional dysregulation might be the most prominent for some adults with the disorder.

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, with 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 an 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 bidirectional 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 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, some obese ADHD patients may have an underlying eating disorder, such as binge-eating, which has been associated with obesity in prospective studies. Also, lisdexamfetamine 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.

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 as to allow only a few foods to be eaten 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 the 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 do network very well. On a scale of one to 10where 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 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 organizations 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 AdolescPsychiatr 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. This 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 inattentive people are more likely to have accidents that lead to injuries.

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When we don't pay attention, we can put ourselves in dangerous situations. So, 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 on how to 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.

Does this 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.

A recent CNN report, http://tinyurl.com/yannlfd6, highlighted a paper published in Pediatrics, which reported that pregnant women who use acetaminophen during pregnancy put their unborn child at two-fold increased risk for attention deficit hyperactivity disorder (ADHD).    In that study, acetaminophen use during pregnancy was common;  nearly half of women surveyed used the painkiller during pregnancy.   Other studies have reported similar associations of acetaminophen, also known as paracetamol with ADHD or with other problems in childhood (e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300094/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177119/,  https://www.ncbi.nlm.nih.gov/pubmed/24566677,  https://www.ncbi.nlm.nih.gov/pubmed/24163279). Given these prior findings, it seems unlikely that the new report is a chance finding.  But does it make any biological sense?   One answer to that question came from an epigenetic study.  Such studies figure out if assaults from the environment change the genetic code.  One epigenetic study found that prenatal exposure changes the fetal genome via a process called methylation.  Such genomic changes could increase the risk for ADHD (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540511/). Because all of these studies are observational studies, one cannot assert with certainty that there is a causal link between acetaminophen use during pregnancy. 

The observed association could be due to some unmeasured third factor.  Although the researchers did a respectable job ruling out some third factors, we must acknowledge some uncertainty in the finding.  That said, what should pregnant women do if they need acetaminophen.   I suggest you bring this information to your physician and ask if there is a suitable alternative.

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 painkillers, 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 the 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 aweak, yet real, the 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 usecausedtheir 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 for risks to make an informed decision.

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