CHAPTER 18 Attention-Deficit/Hyperactivity Disorder Michael I. Reiff, MD, FAAP Introduction Overactive children were described in the medical literature over a century ago. In 1902, George Still observed a pattern of behavior in children that consisted of restlessness, inattentiveness, and over-arousal with an inability to internalize rules and limits. As a reflection of the Victorian era, he attributed the condition to a defect in moral character.1 Children who recovered from influenza encephalitis following the endemic of 1917–1918 often displayed symptoms of restlessness, inattention, impulsivity, easy arousability, and hyperactivity. This was described as a postencephalitic behavior disorder.2 Research in neuropsychology, coupled with clinical observations, led to progressive changes in the name of the condition from hyperkinetic impulse disorder to attention deficit disorder and, most recently, to attention-deficit/hyperactivity disorder (ADHD). The core symptoms of ADHD are inattention, hyperactivity, and impulsivity. Attention-deficit/hyperactivity disorder is one of the most common and most extensively studied behavioral disorders in school-aged children. It is a chronic condition of childhood and adolescence and can persist into adulthood.3 Demographics/Epidemiology The prevalence rate of ADHD varies depending on diagnostic criteria, the population studied, and the number of sources used to establish a diagnosis. The absence of biological markers to establish a diagnosis of ADHD and the need to depend on parent and teacher reports of behavior is a challenge to epidemiological research. In a national study, 7% of children met the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for ADHD.4 In this study, fewer than half of children identified with ADHD received either a diagnosis or regular treatment for ADHD. Poor children were more likely to meet criteria for ADHD, whereas wealthier children were more likely to receive regular medication treatment. In studies that use clinical samples, there is a male predominance of ADHD with a male-to-female ratio of 3:1 for the combined type and 2:1 for the predominantly inattentive type.5 In community samples, predominantly inattentive ADHD is the most prevalent subtype (about 1.5 times more common than the combined type).5 School-aged and adolescent girls are more likely to comprise the inattentive subtype.6 Attention-deficit/hyperactivity disorder does occur in preschool children, although the diagnosis is more challenging.7 The International Classification of Diseases, 10th Revision (ICD-10),8 uses the term hyperkinetic disorder. According to this classification, the diagnosis requires the presence of both impaired attention and activity problems; because of this, there is a lower prevalence of ADHD according to the ICD-10 criteria than according to the DSM-5 criteria. Etiology Attention-deficit/hyperactivity disorder is a heterogeneous disorder with a multifactorial etiology. A diverse set of biobehavioral pathways can lead to the behavioral expression of the core symptoms of ADHD.9 Genetic, epigenetic, and environmental factors interact to give rise to the ADHD phenotypes. A multifactorial model integrates genetic, neural, cognitive, and behavioral mechanisms. Behavioral disinhibition has been proposed as the major core deficit in ADHD.10 In this model, children with ADHD are found to have difficulty mobilizing delayed gratification, the ability to interrupt ongoing responses (eg, stopping playing a video game because it is time for homework), and interference control (eg, not reacting to a friend walking past the classroom door while concentrating on a math problem). Meta-analyses of candidate-gene association studies have found strong associations between ADHD and multiple genes involved in dopamine and serotonin pathways.11 The gene most strongly implicated in ADHD is the human dopamine receptor D4 gene.12 In support of this observation, stimulant medications are primarily dopamine reuptake inhibitors. Imbalances in dopaminergic and noradrenergic regulation mediate the core symptoms of ADHD.13–15 These neurotransmitters may increase the inhibitory influences of frontal cortical activity on subcortical structures. Stimulant medications and other medications found effective in ADHD treatment increase the inhibitory influences of frontal lobe activity through these dopaminergic and noradrenergic influences.16,17 Deficits in frontal lobe functioning and subcortical connections with the frontal lobes—particularly the caudate, putamen, and globus pallidus—have been found in neurobiological and neuroimaging studies.18 Neuroimaging studies have also found ADHD to be associated with delays in cortical maturation. Cortical development in children with ADHD lags behind typically developing children by years but follows the normal sequence of brain development. This observation has led to the conclusion that ADHD represents a delay rather than a deviance in cortical brain maturation.19,20 Cortical delay is most prominent in the lateral prefrontal cortex, an area that supports the ability to suppress inappropriate responses, executive control of attention, evaluation of reward contingencies, higher-order motor control, and working memory. These are the domains of neuropsychological functioning that have been found to be impaired in children with ADHD. Measures of brain structure and function in children diagnosed with ADHD overlap significantly with those of the general population and, because of this, are not useful in diagnosis. Attention-deficit/hyperactivity disorder has strong familial associations. Parents and siblings of a child with ADHD carry a 2- to 8-fold increase in the risk for ADHD. Twin studies have found that 75% of the variance in ADHD phenotype can be attributed to genetic factors. If one identical twin has ADHD, the other twin has a greater than 50% chance of having ADHD.21 Biological and psychosocial factors also contribute to meeting criteria for the ADHD diagnosis. Prenatal exposure to alcohol, cocaine, and nicotine are associated with ADHD phenotypes.22 Psychosocial adversity is also an important risk factor. Chronic family conflict, decreased family cohesion, and parental psychopathology have been found to occur more commonly in families of children with ADHD than in controls. Functional Impairment The diagnosis of ADHD and subsequent treatment require evidence of impairment in functioning. Children with ADHD have been found to have significant functional impairment in the areas of academic achievement, family relationships, peer relationships, self-esteem and self-perception, and overall adaptive function.23–25 Although ADHD increases the risk for impairments in learning, social relationships, and adult outcomes, there is a wide variation in how it affects each individual. ADHD is associated with: ■Underachievement in school/work ■Learning disabilities ■Special education classes ■Repeating a grade ■More suspensions ■School drop-out ■Parenting distress ■Perceived incompetence in parenting ■Impairment in parental harmony ■Parent-child interaction problems ■Negative peer ranking of social problems ■Low self-esteem/self-perception ■Difficult peer relationships ■Immature social skills ■Suboptimal participation in community life ■Increased accidental injuries ■Increased automobile accidents Core symptoms of ADHD challenge school-related activities and tasks, relationships, and other functions. Cognitive impairments are mediated by lack of impulse control and deficits in attention, memory, organization, time management, and judgment. Activity limitations include difficulties in learning and applying knowledge (eg, reading, writing, and mathematics), and problems with carrying out single or multiple tasks, studying, and self-managing behavior. Attention-deficit/hyperactivity disorder also impacts interpersonal interactions; communication and self-care; adjusting to and succeeding in educational programs; leaving school to enter work; and establishing a community, social, and civic life. It is these broad functional disabilities, rather than the core diagnostic criteria, that should become targets for intervention in individuals with ADHD.26 Coexisting Conditions The majority of children and adolescents meeting diagnostic criteria for ADHD also have coexisting problems and conditions. The most prevalent conditions include other disruptive behavior disorders (oppositional defiant disorder [ODD] and conduct disorder), anxiety disorder, depressive disorders, and learning disabilities. Sleep disturbances are also common. Each of these conditions adds its own elements to the functional impairment of individuals with ADHD (Table 18.1).
Martin T. Stein, MD, FAAP
Table 18.1. Prevalence of Conditions in Community Samples With and Without Attention-Deficit/Hyperactivity Disorder (ADHD) | ||
| Condition | Coexisting With ADHDa | In Non-ADHD Populationsb |
Oppositional defiant disorder | 35% | 2%-16% (males) |
Conduct disorder | 25% | 6%—16% (males); 2%-9% (females) |
Anxiety disorder | 25% | 5%-10% |
Depressive disorder | 18% | 2% (child); 5% (adolescent) |
Reading disabilityc | 51% boys | 14.5% boys |
a Green M, Wong M, Atkins D, et al. Diagnosis of Attention Deficit/Hyperactivity Disorder. Technical Review 3. Rockville, MD: US Department of Health and Human Services; 1999. Agency for Health Care Policy and Research (AHCPR) publication 99–0050.
b Lewis MB, ed. Child and Adolescent Psychiatry: A Comprehensive Textbook. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.
c Yoshimasu K, Barbaresi WJ, Colligan RC, et al. Gender, ADHD, and reading disability in a population-based birth cohort. Pediatrics. 2010;126(4):e788–e795.
In addition to coexisting with ADHD, many disorders can mimic ADHD, with presenting concerns about inattention, including learning disabilities, intellectual disabilities, autism spectrum disorder, anxiety, depression, seizure disorders, sleep disorders, central nervous system trauma or infection, hyperthyroidism, sexual abuse, and substance abuse. ADHD criteria can also be met as part of the presentations of fragile X syndrome, fetal alcohol spectrum disorder, and Tourette disorder.27 The presence of a coexisting condition can substantially change predictors of outcomes and influence the targets for treatment. For example, children with ADHD and coexisting ODD are at risk for developing conduct disorder, which can be a gateway to adolescent substance abuse.28 Children with ADHD and coexisting mood disorders may have a poorer outcome during adolescence than children with ADHD alone. Children with coexisting anxiety disorders may differ in their response to stimulant medication and, in some cases, may respond just as well to behavioral treatments as to medication management.29 Children and adolescents with ADHD and coexisting academic problems may benefit from accommodative services under Section 504 of the Rehabilitation Act or for more intensive special education services under the Individuals with Disabilities Education Act (IDEA), depending on the extent of their academic problems.30
Prognosis
The long-term outcome for children with ADHD is related to the severity and type of symptoms, coexisting conditions (eg, mental health disorders and learning disabilities), cognitive abilities (IQ), family situation, and treatment. Nearly one-third of children with ADHD will continue to fulfill norm-referenced criteria for ADHD as adults, and the majority will have at least one mental health disorder in adulthood.31 Hyperactivity tends to diminish over time, but impulsivity and inattention often persist. Adolescents with ADHD often display immature peer interactions.32
It is important to recognize that most follow-up studies of children with ADHD do not evaluate the effects of treatment strategies. The longest systematic evidence based follow-up to date is the 14-month outcome Multimodal Treatment Study of Children with ADHD (MTA).33 This study found that carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. At 14 months, 68% of students who had received the extensive behavioral and medication interventions in the study protocol appeared “normalized” on behavior rating scales filled out by their teachers. This was contrasted with 56% receiving only the strict medication component and 34% receiving only the extensive behavioral interventions in the study protocol. The combined therapy was also superior for treating children with low socioeconomic status and with coexisting anxiety.33
Follow-up of the MTA cohort 6 to 8 years after the trial, when the original participants were 13 to 18 years of age, showed that the original study groups had not continued to receive their randomly assigned treatment and did not differ significantly from each other with respect to any variables, including grades, arrests, and psychiatric hospitalizations. The study participants were actually found to demonstrate worse outcomes than local age-matched, normative comparison groups. The best predictors of functioning in these subjects, now that they were adolescents, were the severity of symptoms at enrollment, the socioeconomic status of the participant’s family, and the degree of the individuals’ response to any of the initial assigned study treatments.34
The adult follow-up study of the children in the MTA cohort (mean age 25 years) showed that functional outcomes (educational, occupational, legal, emotional, substance use disorder, and sexual behavior) among the children treated for ADHD compared to community controls varied; outcomes were generally worse when ADHD symptoms persisted. Initial ADHD symptom severity, parental mental health, and childhood comorbidity affected persistence of ADHD symptoms into adulthood.35 One possible interpretation of these results is that in the absence of systematic, regular, follow-up, gains from an optimal treatment plan may deteriorate.
Adolescents with ADHD have more driving violations and more motor vehicle accidents, including accidents with fatalities. They also initiate intercourse sooner, with more sexual partners, and use birth control less often; they have more sexually transmitted infections and more teenage pregnancy. Teenagers with ADHD smoke at a younger age and have a higher prevalence of smoking. Those with conduct disorders are at increased risk for substance abuse. The risk of substance use disorders over the lifespan is up to twice as great in individuals with ADHD. Adolescent girls with ADHD have more depression, anxiety, poor teacher relationships, and impaired academic performance compared with their peers. Compared with boys with ADHD, they are more impaired by self-reported anxiety, distress, depression, and an external locus of control.36
Attention-deficit/hyperactivity disorder is associated with academic underachievement in reading and impaired school functioning.37 Children and adolescents with ADHD have greater rates of school absenteeism, grade retention, and school dropout. They are more frequent users of school-based services and have increased rates of detention and expulsion.23 Coexisting learning disabilities and psychiatric disorders add to the magnitude of poor school outcomes. Although students may be doing well on stimulant medications, medication treatment does not necessarily improve standardized test scores or ultimate educational attainment. Stimulant treatment has been associated with a significant decrease in the rate of substance abuse disorder,37 although some recent studies have challenged this effect of treatment.38
Studies of adults with ADHD suggest that they have lower socioeconomic status, more work difficulties, and more frequent job changes, as well as fewer years of education and lower rates of professional employment. Adults with ADHD also report more psychological maladjustment, more speeding violations and suspension of drivers’ licenses, poorer work performance, and more frequent quitting or being fired from jobs.39
Diagnosis and Evaluation
Hyperactivity, impulsivity, and inattention are observed in many children and adolescents during typical development. Attention-deficit/hyperactivity disorder is considered only when the symptoms are persistent and pervasive (present in multiple environments) and impair critical functions of learning and social development consistent with a child’s developmental age. Most studies of children meeting criteria for ADHD include only school-aged children and adolescents. The diagnostic challenge to define ADHD in preschool children is significant in that, to some degree, all behaviors associated with ADHD are part of normal development in the preschool age group.
Unlike most medical conditions, but similar to other behaviorally defined disorders, there are no biological tests or imaging studies that can be used to diagnose ADHD. Instead, the diagnostic criteria from the DSM, an empirically based classification system of behavior disorders, are recommended as the framework for primary pediatric health care professionals’ clinical assessment of ADHD. The DSM facilitates communication among professionals and patients, provides information relevant to treatment and prevention, and encourages research in understanding behavioral problems that impact development.
Diagnostic criteria for ADHD in school-aged children and adolescents include documentation of the following:
1.Several symptoms present before age 12 years.
2.Symptoms present in 2 or more major settings.
3.Symptoms cause significant difficulty in functioning.
4.Adolescents can meet less criteria than children.
5.Criteria consider functioning by asking for severity. (The DSM, however, is not helpful regarding how to determine level of functioning at any developmental stage.)
6.Significant impairments in learning and/or social interactions.
7.Symptoms are not attributable to another mental health condition.
Eighteen specific behaviors must be ascertained as a part of the diagnostic process using the DSM-5. Three subtypes of ADHD (predominantly hyperactive-impulsive type, predominantly inattentive type, and combined type) are delineated.3
The diagnostic process must include ascertainment of how many of the 18 ADHD-associated behaviors occur frequently and in most situations. The DSM for Primary Care is a guide to distinguish normal developmental variation from the behaviors associated with ADHD.40 Documenting that the behaviors occur frequently is the first step toward good practice. One significant shortfall of the DSM, with the exception of allowing adolescents to meet diagnostic standards with only 5 inattentive and/or hyperactive/impulsive criteria instead of the 6 required for children, is that it is not developmentally sensitive. In contrast, preschoolers may display many more of these criteria as part of their normal development.
A clinician must establish whether the behaviors are limited to a particular environment or situations only, or whether the behaviors are present in a variety of situations. There must be evidence that core ADHD behaviors occur across a child’s major environments, including home and school. Knowledge about behaviors in social activities outside of school and home (eg, during sports, camp, scouting, or religious activities) may also be useful. If a child is exhibiting ADHD symptoms only at school but not at home or in any other settings, the symptoms may not represent ADHD but might be secondary to a primary language, learning, or intellectual disability. Alternatively, if the child is exhibiting the ADHD symptoms only at home, not at school or any other setting, a parental-child interaction problem, developmentally inappropriate parental expectations or limit-setting, or parental psychopathology may be the primary cause of these symptoms. Inattentive behaviors may also be the result of problems with hearing, vision, anxiety, depression, allergic rhinitis, or obstructive sleep disorders. Ascertain-ing that the duration of symptoms is longer than 6 months is crucial. Many of the 18 ADHD symptoms may occur in response to life event changes (eg, marital discord, divorce, economic stress, a family move, a new school, or an illness in a family member) or during the early stages of a disease process (eg, posttraumatic encephalopathy, petit mal seizures, acquired hearing loss, or adrenoleukodystrophy). Chronic problems, such as living in poverty or enduring ongoing physical abuse or significant emotional neglect, may also produce symptoms indistinguishable from ADHD.
Symptoms of ADHD that are not associated with impairments in schoolwork or with successful social relationships do not meet the diagnostic criteria for ADHD. An inadequate assessment of functional impairment is a common cause of overdiagnosis. For example, the hyperactivity, impulsivity, or inattentiveness in some school-aged children is either not severe enough or is situational in an educational or social environment but not at home. Overactivity and situational inattentiveness in a school-aged child who is doing well in the classroom, achieving academically, and socially engaging is not ADHD. Clinical judgment is important in assessing the effect of the core ADHD symptoms on academic achievement, classroom performance, family life, social skills, independent functioning, self-esteem, leisure activities, and self-care. Asking a parent or teacher, “Do you think that Billy’s inattention and hyperactivity are impairing his school performance or peer interactions?” can help to establish the presence of functional impairment.
An evidence-based practice guideline for the diagnosis of school-aged children with ADHD has been published by the American Academy of Pediatrics (AAP).41 Following is a summary of the guidelines.
Recommendation 1: In a child 6 to 12 years old who presents with inattention, hyperactivity, impulsivity, academic underachievement, or behavior problems, primary care clinicians should initiate an evaluation for ADHD.
Early recognition of ADHD by primary pediatric health care professionals is ensured when screening for core symptoms and problems in school and social relationships occurs during health supervision visits. The AAP practice guideline suggests the following screening questions:
1.How is your child doing in school?
2.Are there any problems with learning that you or the teacher have seen?
3.Is your child happy in school?
4.Are you concerned with any behavioral problems in school, at home, or when your child is playing with friends?
5.Is your child having problems completing classwork or homework?
Recommendation 2: The diagnosis of ADHD requires that a child meet DSM-5 criteria.
AUTHORS’ CLINICAL COMMENTARY
This recommendation can pose a problem for the clinician. Consider the child or adolescent who is experiencing significant functional disability in significant areas but falls short of meeting full criteria for the ADHD diagnosis. The authors suggest that clinical judgment of the presence of significant functional disabilities should override strict adherence to DSM criteria in these situations because access to treatments, such as medication management, are contingent on receiving the ADHD diagnosis, as is likely the family’s insurance coverage for the visit.
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