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The diagnosis of ADHD should only be done by a licensed clinician, and that clinician should have one goal in mind: to plan a safe and effective course of evidence-based treatment. The infographic gives a summary of this diagnostic approach which my colleagues and I prepared for our "Primer" about ADHD,http://rdcu.be/gYyV.  A key point that parents of ADHD youth and adults with ADHD should keep in mind is that there is only one way to diagnose ADHD.An expert clinician must document the criteria for the disorder as specified by either the Diagnostic and Statistical Manual of the American Psychiatric Association, which is now in its fifth edition (DSM-5), or the World Health Organization's International Classification of Diseases (ICD-10). The two sets of criteria are nearly identical. These criteria are most commonly applied by a clinician asking questions of the parent (for children) and/or patient (for adolescents and adults).For children, information from the teacher can be useful. Some clinicians get this information by having the parent ask the teacher to fill out a rating scale. This information can be very useful if it is available.  When diagnosing adults, it is also useful to collect information from a significant other, which can be a parent for young adults or a spouse for older adults. But when such informants are not available, diagnosing ADHD based on the patient's self-report is valid. As the infographic indicates, any diagnosis of ADHD should also assess for comorbid psychiatric disorders, as these have implications for which ADHD medications will be safe and effective. And because a prior history of cardiovascular disease or seizures frequently contraindicate stimulants. These must also be assessed.

There is a growing interest (and controversy) in 'adult-onset ADHD. No current diagnostic system allows for the diagnosis of ADHD in adulthood, yet clinicians sometimes face adults who meet all criteria for ADHD, except for age at onset. Although many of these clinically referred adult-onset cases may reflect poor recall, several recent longitudinal population studies have claimed to detect cases of adult-onset ADHD that showed no signs of ADHD as a youth (Agnew-Blais, Polanczyk et al. 2016, Caye, Rocha, et al. 2016). They conclude, not only that ADHD can onset in adulthood, but that childhood-onset and adult-onset ADHD may be distinct syndromes(Moffitt, Houts, et al. 2015)

In each study, the prevalence of adult-onset ADHD was much larger than the prevalence of childhood-onset adult ADHD). These estimates should be viewed with caution.  The adults in two of the studies were 18-19 years old.  That is too small a slice of adulthood to draw firm conclusions. As discussed elsewhere (Faraone and Biederman 2016), the claims for adult-onset ADHD are all based on population as opposed to clinical studies.
Population studies are plagued by the "false positive paradox", which states that, even when false positive rates are low, many or even most diagnoses in a population study can be false.  

Another problem is that the false positive rate is sensitive to the method of diagnosis. The child diagnoses in the studies claiming the existence of adult-onset ADHDused reports from parents and/or teachers but the adult diagnoses were based on self-report. Self-reports of ADHD in adults are less reliable than informant reports, which raises concerns about measurement error.   Another longitudinal study found that current symptoms of ADHD were under-reported by adults who had had ADHD in childhood and over-reported by adults who did not have ADHD in childhood(Sibley, Pelham, et al. 2012).   These issues strongly suggest that the studies claiming the existence of adult-onset ADHD underestimated the prevalence of persistent ADHD and overestimated the prevalence of adult-onset ADHD.  Thus, we cannot yet accept the conclusion that most adults referred to clinicians with ADHD symptoms will not have a history of ADHD in youth.

The new papers conclude that child and adult ADHD are "distinct syndromes", "that adult ADHD is more complex than a straightforward continuation of the childhood disorder" and that adult ADHD is "not a neurodevelopmental disorder". These conclusions are provocative, suggesting a paradigm shift in how we view adulthood and childhood ADHD.   Yet they seem premature.  In these studies, people were categorized as adult-onset ADHD if full-threshold add had not been diagnosed in childhood.  Yet, in all of these population studies, there was substantial evidence that the adult-onset cases were not neurotypical in adulthood (Faraone and Biederman 2016).  Notably, in a study of referred cases, one-third of late adolescent and adult-onset cases had childhood histories of ODD, CD, and school failure(Chandra, Biederman, et al. 2016).   Thus, many of the "adult onsets" of ADHD appear to have had neurodevelopmental roots. 

Looking through a more parsimonious lens, Faraone and Biederman(2016)proposed that the putative cases of adult-onset ADHD reflect the existence of subthreshold childhood ADHD that emerges with full threshold diagnostic criteria in adulthood.   Other work shows that subthreshold ADHD in childhood predicts onsets of full-threshold ADHD in adolescence(Lecendreux, Konofal, et al. 2015).   Why is onset delayed in subthreshold cases? One possibility is that intellectual and social supports help subthreshold ADHD youth compensate in early life, with decompensation occurring when supports are removed in adulthood or the challenges of life increase.  A related possibility is that the subthreshold cases are at the lower end of a dimensional liability spectrum that indexes risk for onset of ADHD symptoms and impairments.  This is consistent with the idea that ADHD is an extreme form of a dimensional trait, which is supported by twin and molecular genetic studies(Larsson, Anckarsater, et al. 2012, Lee, Ripke, et al. 2013).  These data suggest that disorders emerge when risk factors accumulate over time to exceed a threshold.  Those with lower levels of risk at birth will take longer to accumulate sufficient risk factors and longer to onset.

In conclusion, it is premature to accept the idea that there exists an adult-onset form of ADHD that does not have its roots in neurodevelopment and is not expressed in childhood.   It is, however, the right time to carefully study apparent cases of adult-onset ADHD to test the idea that they are late manifestations of a subthreshold childhood condition.

Although there has been much research documenting that ADHD adults are at risk for other psychiatric and substance use disorders, relatively little is known about whether ADHD puts adults at risk specifically for somatic medical disorders.  

Given that people with ADHD tend toward being disorganized and inattentive, and that they tend to favor short-term over long-term rewards, it seems logical that they should be at higher risk for adverse medical outcomes.  But what does the data say?

In a systematic review of the literature, Instances and colleagues have provided a thorough overview of this issue.  Although they found 126 studies, most were small and were of "modest quality".   Thus, their results must be considered to be suggestive, not definitive for most of the somatic conditions they studied.  

Also, they excluded articles about traumatic injuries because the association between ADHD and such injuries is well established. Using qualitative review methods, they classified associations as being a) well-established; b) tentative, or c) lacking sufficient data.

Only three conditions met their criteria for being a well-established association: asthma, sleep disorders, and obesity.  

They found tentative evidence implicating ADHD as a risk factor for three conditions: migraine headaches, celiac disease, and diseases of the circulatory system.  

These data are intriguing, but cannot tell us why ADHD people are at increased risk for somatic conditions. One possibility is that suffering from ADHD symptoms can lead to an unhealthy lifestyle, which leads to increased medical risk. Another possibility is that the biological systems that are dysregulated in ADHD are also dysregulated in some medical disorders.  For example, we know that there is some overlap between the genes that increase the risk for ADHD and those that increase the risk for obesity. We also know that the dopamine system has been implicated in both disorders.

Instances and colleagues also point out that some medical conditions might lead to symptoms that mimic ADHD. They give sleep-disordered breathing as an example of a condition that can lead to the symptom of inattention.    

But this seems to be the exception, not the rule. Other medical conditions co-occurring with ADHD seem to be true comorbidities, rather than the case of one disorder causing the other. Thus, primary care clinicians should be alert to the fact that many of their patients with obesity, asthma, or sleep disorders might also have ADHD.  

By screening such patients for ADHD and treating that disorder, you may improve their medical outcomes indirectly via increased compliance with your treatment regime and an improvement in health behaviors. We don't yet have data to confirm these latter ideas, as the relevant studies have not yet been done.

If you've ever wondered how experts make treatment recommendations for patients with ADHD, take a look at this ADHD treatment decision tree that my colleagues and I constructed for our "Primer" about ADHD,http://rdcu.be/gYyV.  

Although a picture is worth a thousand words, keep in mind that this infographic only gives the bare bones of a complex process. That said, it is telling that one of the first questions an expert asks is if the patient has a comorbid condition that is more severe than ADHD. The general rule is to treat the more severe disorder first and after that condition has been stabilized plan a treatment approach for the other condition. Stimulants are typically the first-line treatment due to their greater efficacy compared with non-stimulants.

When considering any medication treatment for ADHD safety is the first concern, which is why medical contraindications to stimulants, such as cardiovascular issues or concerns about substance abuse, must be considered. For very young children (preschoolers) family behavior therapy is typically used before medication. Clinicians also must deal with personal preferences.  Some parents and some adolescents and adults with ADHD simply don't want to take stimulant medications for the disorder. When that happens, clinicians should do their best to educate them about the costs and benefits of stimulant treatment.

If, as is the case for most patients, the doctor takes the stimulant arm of the decision tree, he or she must next decide if methylphenidate or amphetamine is more appropriate. Here there is very little guidance for doctors. Amphetamine compounds are a bit more effective, but can lead to greater side effects.  Genetic studies suggest that a person's genetic background provides some information about who will respond well to methylphenidate, but we are not yet able to make very accurate predictions. After choosing the type of stimulant, the doctor must next consider what duration of action is appropriate for each patient.

There is no simple rule here; the choice will depend upon the specific needs of each patient. Many children benefit from longer-acting medications to get them through school, homework, and late afternoon/evening social activities. Likewise for adults. But many patients prefer shorter-acting medications, especially as these can be used to target specific times of day and can also lower the burden of side effects.  

For patients taking down the non-stimulant arm of the decision tree, duration is not an issue but the patient and doctor must choose from among two classes of medications norepinephrine reuptake inhibitors or alpha-2-agonists. There are not a lot of good data to guide this decision but, again, genetics can be useful in some cases. Regardless of whether the first treatment is a stimulant or a non-stimulant, the patient's response must be closely monitored as there is no guarantee that the first choice of medication will work out well. In some cases, efficacy is low, or adverse events are high. Sometimes this can be fixed by changing the dose, and sometimes a trial of a new medication is indicated.

If you are a parent of a child with ADHD or an adult with ADHD, this trial-and-error approach can be frustrating. But don't lose hope. In the end, most ADHD patients find a dose and a medication that works for them. Last but not least, when medication leads to a partial response, even after adjusting doses and trying different medication types, doctors should consider referring the patient for a non-pharmacologic ADHD treatment.

You can read details about these in my other blogs, but here the main point is to find an evidence-based treatment. For children, the biggest evidence base is for behavioral family therapy. For adults, cognitive behavior therapy (CBT) is the best choice.  Except for preschoolers, the experts I worked with on this infographic did not recommend these therapies before medication treatment. The reason is that the medications are much more effective, and many non-pharmacologic treatments (such as CBT) have no data indicating they work well in the absence of medication.

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.