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Eric Mick, ScD, Stephen V. Faraone, PhD, Joseph Biederman, MD, and Thomas J. Spencer, MD

Primary Psychiatry. 2004;11(7):42-48

 

Faculty Affiliations and Disclosures

Dr. Mick is assistant professor of psychiatry at Harvard Medical School and assistant director of research in the Pediatric Psychopharmacology Research Unit at Massachusetts General Hospital, both in Boston, Massachusetts.

Dr. Faraone is professor in the Department of Epidemiology at Harvard School of Public Health, clinical professor of psychiatry at Harvard Medical School, and director of research in the Pediatric Psychopharmacology Research Unit at Massachusetts General Hospital, all in Boston.

Dr. Biederman is professor of psychiatry at Harvard Medical School and chief of the Pediatric Psychopharmacology Research Unit at Massachusetts General Hospital.

Dr. Spencer is associate professor of psychiatry at Harvard Medical School and assistant chief of the Pediatric Psychopharmacology Research Unit at Massachusetts General Hospital.

Disclosure: Dr. Mick is a consultant for Janssen, receives grant and/or research support from the National Institute of Mental Health, and receives honoraria and/or expenses from Ortho-McNeil. Dr. Faraone is a consultant for Eli Lilly, Noven, Ortho-McNeil, and Shire; serves on the speaker’s bureaus for Eli Lilly, Ortho-McNeil, and Shire; and receives research support from Eli Lilly, National Institute of Child Health and Development, National Institute of Mental Health, National Institute of Neurological Diseases and Stroke, Ortho-McNeil, and Shire. Dr. Biederman serves on the speaker’s bureaus for Cephalon, Eli Lilly, Novartis, Ortho-McNeil, Pfizer, Shire, and Wyeth; receives research support from Cephalon, Eli Lilly, Janssen, National Institute of Child Health and Human Development, National Institute on Drug Abuse, National Institute of Mental Health, Novartis, Pfizer, Shire, the Stanley Foundation, and Wyeth; and is on the advisory boards of CellTech, Cephalon, Eli Lilly, Janssen, Johnson & Johnson, Novartis, Noven, Ortho-McNeil, Pfizer, and Shire. Dr. Spencer is a consultant for, serves on the speaker’s bureaus of, and receives grant and/or research support from Abbott, Alza, Boston Life Sciences, Bristol-Myers Squibb, Cephalon, CellTech, Eisai, Eli Lilly, GlaxoSmithKline, Gliatech, Novartis, Ortho-McNeil, Pfizer, Shire, Solvay, and Wyeth.

Funding/support: This work was supported in part by a grant from the National Institute of Mental Health (grant #R01 MH57934) and by funds from Ortho-McNeil.

Please direct all correspondence to: Eric Mick, ScD, WACC 725, Pediatric Psychopharmacology Research Unit, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St, Boston, MA 02114; Tel: 617-724-0956; Fax: 617-724-3742.

 

Focus Points

• Attention-deficit/hyperactivity disorder (ADHD) is a childhood disorder with a chronic course that is associated with impairment in functioning over time.

• ADHD is a developmental disorder that presents differently during advancing levels of maturation with declining overt symptoms of hyperactivity/impulsivity and continuing symptoms of inattention.

• Although the diagnostic criteria for ADHD have evolved over several decades, developmentally appropriate criteria for older adolescents and adults need to be developed and validated.

 

Abstract

This review details the history of attention-deficit/hyperactivity disorder (ADHD) and examines the current longitudinal studies of ADHD that have followed children into adolescence or adulthood. These longitudinal follow-up studies have been hampered by the changing diagnostic criteria for the disorder. Initiated decades ago, such studies have provided much information regarding the course of the disorder but cannot definitively document the rate of persistence of ADHD because they were heavily influenced by the diagnostic requirement of hyperactivity. According to recent work examining the impact of symptom expression, symptoms of hyperactivity and impulsivity tend to subside earlier than symptoms of inattention, such that the persistence of the disorder into adolescence or adulthood may depend largely on continuing symptoms of inattention. Furthermore, subjects with a remitting course or a residual form of the disorder may continue to present with functional impairments. Thus, criteria for defining persistence of ADHD may need refinement in order to diagnose ADHD in individuals with more mature levels of development.

 

Introduction

Over time, the perception that attention-deficit/hyperactivity disorder (ADHD) is a syndrome of childhood misbehavior that wanes throughout puberty and adolescence has been challenged by volumes of research and a continual refining of standardized diagnostic criteria. Consequently, documenting the course of the disorder is an important step for understanding the significance and therapeutic needs of this psychiatric condition. As such, this review details the history of the disorder and the current longitudinal studies that have followed ADHD children into adolescence or adulthood. This article focuses specifically on the impact of the changing operational definition of the disorder (the reliance on hyperactivity), the impact of normal developmental maturation on recognizing problem behaviors at different ages, and the clinical significance of the diagnosis in older or adult subjects.

 

Definition and Diagnostic Criteria

ADHD, as well as all of the core symptoms associated with it, has long been considered a behavioral disorder of childhood, even if it has not been diagnostically labeled as such over the years. In the 1930s, the symptoms of hyperkinesis, impulsivity, learning disability, and short attention span were described as “minimal brain damage” and later as “minimal brain dysfunction” because these symptoms mimicked those seen in patients with frank central nervous system injuries. In the 1950s, this label was modified to “hyperactive child syndrome,” with the eventual inclusion of “hyperkinetic reaction of childhood” into the Diagnostic and Statistical Manual of Mental Disorders, Second Edition (DSM-II),1 in 1968. Each of these labels and sets of criterion were focused exclusively on children and placed the largest importance on hyperactivity and impulsivity as hallmarks of the disorder. Although the section of the DSM-II dedicated to hyperkinetic reaction of childhood was very brief and unstructured, it persisted as the prevailing standard until the publication of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III),2 in 1980.

The DSM-III presented a significant change in the description of the disorder and was the first to formally recognize inattention as a significant component of the disorder. The DSM-III definition also recognized developmental variability and indicated that this variability played a role in the presentation of the disorder in individuals of different ages. Most importantly for this discussion, the DSM-III included a residual type of ADHD that could be diagnosed in individuals with a history of meeting full criteria for the disorder, but who presented with a reduced set of symptoms, if the remaining symptoms continued to cause significant levels of impairment. Although the revision of the DSM-III (DSM-III-R)3 published in 1987 eliminated the residual type of ADHD, it returned in 1994 with the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),4 that also offered criterion for specific subtypes of ADHD marked by inattention, hyperactivity/impulsivity, or both core features of the disorder.

As the field has struggled with characterizing ADHD for the past several decades, there has been a consistent underlying notion that ADHD is not a completely remitting condition in all cases. The emphasis primarily on hyperactivity in earlier years has been shown to impact the rates of persistence of the disorder in prospective follow-up studies of the longest duration.

 

ADHD Course in Childhood

There has been relatively little debate that once diagnosed, ADHD persists throughout childhood in a majority of cases. For example, in an epidemiological sample, Lambert and colleagues5 found that 43% of subjects were still treated for hyperactivity 3–4 years after their initial assessment. Similarly, Taylor and colleagues6 found that 63% of children with ADHD met criteria after 9 months, Hart and colleagues7 found that 62% of children with ADHD continued to have the full syndrome 1 year later, Biederman and colleagues8 found that 85% of ADHD boys met criteria with impairment after 4 years, and Barkley and colleagues9 found that 72% of boys with ADHD continued to meet criteria after 8 years. Studies reporting that ADHD is almost entirely remitting by adulthood10 found that 68% of hyperactive children reported retrospectively that they had met DSM-III2 ADHD criteria at some point during adolescence. Considering that ADHD typically has an onset at a very young age, these estimates of persistence throughout childhood indicate that the children diagnosed with the disorder will live with it for a sizable proportion of early and school-age development periods.

With the rapid rate of development in school-age years, even 1 year of clinically-significant hyperactivity, impulsivity, or inattention may cause serious disruption of maturation and have long-lasting effects. This hypothesis is supported by many studies in which researchers have consistently shown that ADHD is predictive of a wide range of negative short- and long-term outcomes, including higher rates of behavioral, mood, and anxiety disorders; antisocial and drug abuse disorders; family conflict; impaired school, cognitive, and psychosocial functioning; and educational and vocational disadvantage.10-14

 

Impact of Normal Development on ADHD Symptom Expression

Much of the difficulty in making the diagnosis of ADHD in children arises from the fact that many of the symptoms of ADHD are similar to developmentally appropriate behavior in young children. It is natural for a 4-year-old child to exhibit hyperactivity and impulsivity, for example. The diagnosis of ADHD in very young children then relies on the extent to which reported symptoms are more pronounced or prevalent than other children of the same age. This may impact estimates of duration and definitions of chronic ADHD because as children normally outgrow much of the hyperactivity and impulsivity, the degree to which these symptoms continue to be of primary concern in making the diagnosis may also decline.

Biederman and colleagues15 specifically addressed the relative rate of decline of the core symptoms of ADHD from childhood into early adulthood to offer a developmental perspective on symptom decline. As seen in Figure 1,15 the researchers found a differential rate of symptomatic decline for inattention and hyperactivity/impulsivity. While symptoms of inattention declined at a very modest rate, those of hyperactivity and impulsivity remitted much more abruptly. This work demonstrated that even in a sample of ADHD children with a high rate of persistence,8 overt symptoms of hyperactivity tend to decline with increasing age. Hart and colleagues7 also documented a similar pattern of ADHD-subtype specific persistence: the mean number of hyperactive/impulsive symptoms declined with age while the mean number of inattentive symptoms remained stable from 8–15 years of age. Thus, it appears that the persistence of ADHD is contingent upon continued inattention more than overt hyperactivity or impulsivity.

This is not to say that adolescents and adults do not report subjective feelings of hyperactivity or impulsivity. The criteria listed in the DSM-IV4 and its predecessors were geared toward diagnosing children because many of the symptoms required for a full diagnosis included overt hyperactive/impulsive behaviors. For example, adults with ADHD may be much less likely to get up from their seat and move around the room during a business meeting than children with ADHD would be to get out of their seat and run around a classroom. In contrast, older adolescents and adults with ADHD may report the subjective feeling of wanting to move around or fidget but are able to control the actual behavior. Thus, good estimates of the persistence of ADHD have been lacking because the criteria for ADHD are not developmentally appropriate for older children, adolescents, or adults.

Barkley16 has proposed modified criteria for ADHD in adults that take developmental maturation into account and has suggested that ADHD be recast as a norm-referenced rather than criterion-referenced diagnosis. From this perspective, the diagnosis of ADHD should be dealt with as is the construct of intelligence. One would not have adults complete the Wechsler Intelligence Scales for Children and then conclude that intelligence increases with age. Instead, different test batteries are used for different age groups and, within a single battery, scores are considered high or low in reference to other testers of the same age.

This approach has been used in a study following 148 hyperactive children for 15 years.17 At a mean of 21 years of age, self-reports from these subjects found only 3% meeting criteria for DSM-III-R3 ADHD. The use of a psychometric criterion to define ADHD (symptoms exceeding the 93rd percentile of severity of the control group) resulted in 25% of the sample meeting criteria for ADHD. The clinical significance of the persistent ADHD symptoms was confirmed by parental reports suggesting that 42% of the grown-up ADHD children still met criteria for the disorder.

 

Follow-Up Studies of ADHD

A relatively large number of studies have been published that estimate the persistence of ADHD throughout adolescence and adulthood. The pertinent results from each these studies are presented in the Table.5,7-9,17-33 It is at first apparent that the rate of ADHD at follow-up varies considerably from one study to the next. For example, Mannuzza and colleagues18 reported that at follow-up, 4% of previously hyperactive boys continued to have ADHD, while Hart and colleagues7 found that 85% of ADHD cases continued to meet criteria for ADHD at follow-up. This should not be surprising considering the significant heterogeneity between these studies in the diagnostic criteria employed, the duration of follow-up, and the age of the sample at follow-up. Most important among these variables is age at follow-up—certainly a 5-year follow-up of 12-year-old children will result in a higher prevalence of ADHD than a 5-year follow-up of 25-year-old adults.

Hill and Schoener34 used this level of the heterogeneity in order to estimate the expected rate of ADHD in older populations. They conducted a secondary data analysis with the published data from a subset of the studies presented in the Table. They selected those studies in which the original diagnoses were made concurrently with the creation of the studies’ baseline in childhood, and in which the follow-up reported the persistence of standardized assessments of ADHD. Hill and Schoener34 fit a model to these data that predicted an exponential decline in the rate of ADHD and estimated the rate of adult ADHD to range from approximately 0.8% at 20 years of age to 0.05% at 40 years of age. At first glance, these results appear to provide strong support for the idea that ADHD is, essentially, a remitting disorder.

However, the long-term follow-up studies included may underestimate the persistence of ADHD in older subjects because of the diagnostic criteria employed in defining the sample. Any samples ascertained before the publication of the DSM-III relied on earlier definitions that highlighted hyperactivity as a hallmark of ADHD. Since it is hyperactivity that wanes earliest, it may be that older samples were enriched with subjects more likely to remit from ADHD than individuals identified today. In fact, this hypothesis was born out in the data. A combined estimate of the persistence of ADHD is shown in the Table. The persistence rate was lowest in studies ascertained according to DSM-II1 attention-deficit disorder and highest in those studies ascertained according to DSM-III-R3 ADHD.

In addition, Hill and Schoener34 used a very narrow definition of persistence (ie, continuing to meet full diagnostic criteria). This definition of remission may not be ideal because it does not take into account the full clinical picture of the patient. For example, consider the ADHD child who, as an adult, has one symptom less than that required by the DSM-IV4 but who still experiences substantial distress and disability from the ADHD symptoms that remain. Most clinicians would not define that adult as remitted and would seriously consider the continuation of anti-ADHD treatment.

Biederman and colleagues15 have employed different levels of remission—syndromatic, symptomatic, and functional—to study the age-dependent decline in the prevalence of ADHD.15 Syndromatic remission refers to the loss of full diagnostic status, symptomatic remission refers to the loss of partial diagnostic status, and functional remission refers to the loss of partial diagnostic status plus functional recovery (ie, full recovery). Functional remission is the desired outcome whether it is due to treatment or natural course of the disorder.

Figure 2 depicts the course of ADHD according to this different conceptualization of persistence.15 In this data, the rate of remission from the full disorder (syndromatic remission) was quite high, with 60% of subjects 18–20 years of age no longer meeting criteria for ADHD.15 However, there was still a considerable number of ADHD symptoms present (symptomatic remission) and the majority of ADHD subjects continued to report low levels of functioning despite remission of the full diagnostic criteria (functional remission).

 

Therefore, Hill and Schoener34 may have been far too optimistic in declaring that the prevalence of ADHD in adult samples was nonexistent. An expanded analysis of the literature supports the notion that in many studies, subjects fail to reach symptomatic remission. Faraone and colleagues (unpublished data, 2004) revisited Hill and Schoener’s analyses,34 and included studies that reported the follow-up rate of residual-type ADHD (analogous to symptomatic remission). It should not be surprising that the inclusion of the less-stringent definition of persistence resulted in higher rates in older subjects. The predicted prevalence of ADHD (for full and residual diagnoses, respectively) was 0.9% and 39% at 40 years of age, 0.2% and 29% at 50 years of age, and 0.04% and 22% at 60 years of age.

 

Related Impairment in Adults with Persistent ADHD

If adult ADHD is a clinically-significant disorder, then ADHD adults should show functional impairments in multiple domains. Several studies suggest this to be true. In an early study, Borland and Heckman20 compared ADHD adults with their non-ADHD siblings. The ADHD adults had lower socioeconomic status, more work difficulties, and more frequent job changes. Morrison and colleagues35,36 compared ADHD adults with psychiatric controls matched for age and sex. The ADHD adults had fewer years of education and lower rates of professional employment. Similarly, others have shown that among patients with substance use disorders, ADHD predicts social maladjustment, immaturity, fewer social assets, lower occupational achievement, and high rates of separation and divorce.37-41

Murphy and Barkley42 compared 172 ADHD adults with 30 non-ADHD adults. The ADHD adults reported more psychological maladjustment, more speeding violations, and more frequent changes in employment. Compared with the non-ADHD adults, more ADHD adults had had their drivers license suspended, had performed poorly at work, and had quit or been fired from their job. Moreover, the ADHD adults were more likely to have had multiple marriages.

Barkley and colleagues43 evaluated the motor vehicle driving knowledge, skills, and negative driving outcomes of older adolescents and young adults with ADHD. The ADHD young adults showed no deficits in driving knowledge. Yet compared with controls, they had elevated rates of speeding citations, suspended licenses, crashes, and accidents causing bodily injury. They were more likely to be rated by themselves and others as having poorer driving habits. In addition, a computer-simulated driving test showed the young adults with ADHD to have more crashes, scrapes, and erratic steering.

Given that academic underachievement is a well-known correlate of ADHD in childhood,44 ADHD adults should presumably have histories reflecting school problems. Several studies have shown this to be so. Biederman and colleagues45,46 demonstrated that compared with control adults, ADHD adults had significantly higher rates of repeated grades, tutoring, placement in special classes, and reading disability. Similarly, Murphy and Barkley42 showed that ADHD adults had histories marked by poorer educational performance and more frequent school disciplinary actions against them. Notably, in addition to showing an increased likelihood of having a history of school failure, Seidman and colleagues47 demonstrated that this could not be accounted for by age, learning disabilities, psychiatric comorbidity, or gender.

The work of Biederman and colleagues46 has shown that the residual diagnosis in adults is clinically meaningful as well. In a sample of 128 referred ADHD subjects of both sexes, the researchers examined psychiatric comorbidity, social functioning, and cognitive functioning in subjects meeting full diagnostic criteria for ADHD with those meeting criteria for residual ADHD. They did not find any meaningful differences between groups based upon the full or residual diagnostic status. For example, differences in current global assessment of function scores between those with full and residual ADHD symptoms were <3 points, with the average score being 54 (moderately impaired). The similarities between these subtypes of adult ADHD support the notion that the subsyndromal adult forms of the disorder are part of the same diagnostic entity, differing only in the absence of some symptoms (likely due to developmental variations in the clinical expression of the disorder).

 

Heterogeneous Outcome in Persistent ADHD

Although the literature provides compelling evidence that the diagnosis of ADHD in childhood predicts persistent ADHD and poor outcome in adolescence, these findings also suggest that such a comprised outcome is not shared by all ADHD children. The discussion thus far has not addressed a related clinical question: can the functioning of ADHD children normalize in the context of persistent ADHD?

Disentangling syndromatic persistence from functional outcome in ADHD youth has important implications. The identification of ADHD youth at highest risk for compromised functional outcome will permit the targeting of scarce societal resources for those at highest need. Similarly, the identification of early antecedents of compromised functional outcome could permit the developing of appropriate early intervention strategies.

Biederman and colleagues48 analyzed data from a 4-year longitudinal study of referred children and adolescents with ADHD, to assess normalization of functioning and its predictors among boys with persistent ADHD. Using indices of emotional, educational, and social adjustment, they found that 20% of children with persistent ADHD functioned poorly at follow-up in all three domains, 20% did well in all three domains, and 60% had intermediate outcomes.48 These findings suggested that the syndromatic persistence of ADHD is not associated with a uniform functional outcome but leads instead to a wide range of emotional, educational, and social adjustment outcomes that can be partially predicted by exposure to maternal psychopathology, larger family size, DSM-III-R psychiatric comorbidity, and impulsive symptoms.48 For example, some adults who may have done quite well academically might have more symptoms associated with impairments in social functioning—ADHD does not necessarily preclude high academic achievement.

This work highlights an important caveat in understanding ADHD as a chronic disorder. Although much of this section has focused on the wide range of functional impairments associated with persistent ADHD, functional impairments are not found in all chronic cases of the disorder. Despite continued symptoms of the disorder, some individuals with ADHD can have a good quality of life and normal levels of function in social, academic/professional, and emotional domains.

Thus, while global levels of impairment may help to validate the condition in older subjects, they should not be considered a diagnostic requirement of the disorder. This is analogous to confusion over the use of a family history in making psychiatric diagnoses. Even in highly familial disorders (eg, ADHD, bipolar disorder, etc.), only a minority of cases will have a relative with the disorder. The same holds true in using impairment in correlated—but not core—domains as a diagnostic requirement for chronic ADHD.

 

Conclusion

Symptoms of ADHD have long been recognized as a behavioral disorder of childhood. Modern diagnostic criteria (as laid out in the DSM-IV4) provide a more flexible structure to diagnose different ADHD subtypes, which may be more developmentally sensitive to older subjects, by defining a predominantly inattentive subtype and a residual subtype of ADHD. However, these criteria may need further refinement in order to define ADHD in individuals with more contextually mature levels of development or in reference to the behavior of other individuals of the same age or developmental group.

Utilizing more developmentally-appropriate measures of ADHD in adolescents and adults reveals that a sizable proportion of children with the disorder will continue to exhibit impairing symptoms of the disorder into adulthood. The impact of ADHD on society is enormous in terms of financial cost, negative effects on self-esteem, stress to families, and impact on academic and vocational activities. Because it is more frequently chronic than episodic, ADHD may be a relatively common psychiatric disorder of adulthood in reference to the current prevalence of other disorders. More research on the prevalence of ADHD in adolescence and adulthood is warranted. PP

 

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