CHAPTER 133

Attention-Deficit/ Hyperactivity Disorder

Andrew J. Barnes, MD, MPH, FAAP, and Iris Wagman Borowsky, MD, PhD, FAAP

Physicians should initiate a thorough evaluation for attention-deficit/ hyperactivity disorder (ADHD) in any child aged 4 to 18 years who exhibits social, academic, or behavioral problems associated with inattention, impulsivity, and hyperactivity. Three types of ADHD are described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5): predominantly inattentive presentation, predominantly hyperactive/impulsive presentation, and combined hyperactive-inattentive presentation. Most children and adolescents with the disorder exhibit symptoms of the combined type. A growing body of evidence suggests that differentiating such subtypes has little bearing on prognosis or management.

The diagnosis of ADHD is based solely on clinical judgment, requiring documentation of sufficiently impairing criteria from the inattentive and/or hyperactive/impulsive domains (Box 133.1). Some symptoms of ADHD must be present before 12 years of age, and several symptoms must persist in at least 2 major contexts of the child’s life (eg, home and school) for at least 6 months. These symptoms must be more frequent and severe than those typical in someone of the same developmental age and must impair the child’s developmental competence, learning, or social interactions. The symptoms should not be better explained by another condition (eg, anxiety). If impairing symptoms occur at sub-diagnostic levels or are associated with a DSM-5 exclusionary condition, a diagnosis of ADHD, not otherwise specified, should be made. Treatment, however, is symptomatic and not specific to subtype.

Transient behavioral variations, challenging temperamental features, and problem-level ADHD-like symptoms that are not frankly disordered or sufficiently impairing are better classified using the framework of The Classification of Child and Adolescent Mental Diagnoses in Primary Care: Diagnostic and Statistical Manual for Primary Care (DSM-PC). Child and Adolescent Version instead of DSM-5 (eg, “Hyperactive/Impulsive Developmental Variation— Middle Childhood: The child plays active games for long periods. The child may occasionally do things impulsively, particularly when excited”). One advantage of the DSM-PC is that it takes into account specific environmental and psychosocial contexts, stressors, and developmental factors that influence children’s behavior.

Epidemiology

Attention-deficit/hyperactivity disorder is the most common neurobehavioral disorder in children. An estimated 4% to 12% of school-age children have ADHD, and there exists a 3:1 predominance of boys in community samples. Over the past 2 decades, ADHD diagnoses have increased; it remains unclear whether this represents a true increase in incidence, secular changes in diagnostic criteria and practices, sociocultural bias, or effects of unspecified environmental factors.

^a Presence of 6 symptoms for patients age 16 years or younger or presence of 5 symptoms for patients age 17 years or older.

Derived from Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Clinical Presentation

Children with ADHD have problems with selective attention and mental stamina for nonrewarding or nonpreferred activities. They often make careless mistakes or fail to pay attention to details. They may be easily distracted and have difficulty starting tasks and concentrating on tasks long enough to complete them. Stopping a preferred activity also can be problematic, and caregivers often note that their children with ADHD overfocus or “get lost” in their favorite activities, such as video games, drawing, or reading. Difficulties following instructions and organizing tasks and activities are also characteristic of ADHD. Poor impulse control manifests as difficulty waiting one’s turn, frequently blurting out responses at inappropriate times, and interrupting or intruding on others. Symptoms of hyperactivity include fidgetiness, excessive talking at inappropriate times, difficulty remaining seated or playing quietly, and subjective feelings of restlessness or impatience in older children and adolescents. Difficulties with social relationships and low frustration tolerance are also common among children with ADHD.

Pathophysiology

The etiology of ADHD is unknown. Interacting genetic, prenatal/ perinatal, environmental/psychosocial, and neurologic factors all play a role. Family studies indicate that first-degree relatives of children with ADHD have a risk of ADHD that is 5 times greater than the risk in the general population. Additionally, measures of behavior and attention are more alike in monozygotic twins than in dizygotic twins of the same sex. The most widely confirmed gene association with ADHD is the 7-repeat allele of the D₄ dopamine receptor gene that, although found in approximately 30% of the general population, is found in 50% to 60% of individuals with ADHD. Prenatal and perinatal risk factors that have been associated with ADHD include in utero exposure to alcohol or cigarettes; extreme preterm birth; brain injury or stroke; and severe early deprivation, neglect, and maltreatment.

Currently, ADHD is conceptualized as a chronic neurodevelopmental-behavioral condition. Patients with frontal lobe lesions have long been known to exhibit severe and intractable inattention, hyperactivity, behavioral disinhibition, and impulsivity. Recent neurodevelopmental research suggests that ADHD is associated with developmental differences in specific frontal and prefrontal regions of the brain involved in executive functions, including organizing, planning, sequencing, selective attention, impulse inhibition, the ability to stick to a plan yet change it as needed (ie, set maintenance), the ability to self-talk through internal rules, and working memory. Several recent studies, some longitudinal, show delayed maturation (ie, myelination delayed) and abnormal activation/inactivation of critical prefrontal circuits and frontostriatal reward-motivation circuits in children and adolescents with ADHD compared with control subjects. Dopamine and norepinephrine are involved in neurotransmission within these brain pathways, and the prefrontal cortex is rich in catecholamine receptors. Psychostimulants can improve ADHD symptoms by increasing the availability of these neurotransmitters in the brain, thereby improving efficiency in attention and motivation circuits. Stimulants seem to primarily increase activity in key areas of the striatum, such as the ventral tegmental area, in turn activating the prefrontal cortex and executive functions.

Differential Diagnosis

The symptoms of ADHD (eg, hyperactivity, inattention, distractibility) can be seen in a variety of other conditions (Box 133.2). Sensory deficits, especially hearing impairment, can imitate attention deficits. Attention-deficit/hyperactivity disorder symptoms are often a component of autism spectrum disorder and other neurodevelopmental conditions, such as neurofibromatosis 1 or Tourette syndrome, co-occurring with typical features of the respective diagnoses, such as impaired social communication in children with autism spectrum disorder. Lead and other heavy metals have dose-related detrimental effects on behavior and development; likewise, chronic iron deficiency can result in or mimic ADHD. Seizure disorders, such as petit mal (ie, absence) or partial complex seizures, may cause altered attention or behavioral changes that can mimic ADHD. Other neurologic disorders that can present with symptoms of ADHD include Wilson disease and adrenoleukodystrophy; however, focal and often progressive neurologic deficits of acute to subacute onset are the hallmarks of these rare conditions, as opposed to the more soft and static neurologic signs of ADHD. Certain medications, such as high-dose corticosteroids, phenobarbital, and theophylline, may cause ADHD-like mental status effects, as can recreational drugs of abuse, including inhalants and marijuana. Hyperthyroidism can cause the hyperactive symptoms of ADHD, but other signs of increased metabolism, such as elevated heart rate, tremors, or weight loss, should be apparent. Exposure to alcohol or drugs in utero has been associated with subtle difficulties with learning and attention as the child develops. Congenital infections, central nervous system infections in early childhood, and traumatic brain injuries may produce behaviors similar to those that occur with ADHD. Sleep disorders, especially sleep apnea, can cause severe behavioral problems that often resolve after definitive treatment of the underlying sleep condition. Severe or chronic psychosocial-environmental stressors, such as bullying, marital discord, unemployment, poverty, homelessness, trauma/maltreatment, substance abuse, and ineffective parenting (eg, overly permissive, overly harsh), can also masquerade as, co-occur with, or exacerbate ADHD.

Children with ADHD have an increased prevalence of co-occurring pathology, which can magnify or overshadow the core symptoms of the disorder. Such pathology includes oppositional defiant disorder (35%), conduct disorder (26%), depressive disorders (18%), anxiety disorders (26%), Tourette syndrome and tics, sleep disorders (especially insomnia), fine motor delay or developmental coordination disorder, speech and language disorders, and specific learning disorders of reading, mathematics, and/or written expression. In adolescents and young adults, aggression, delinquency, and other antisocial behaviors, as well as substance abuse, often are seen together with untreated or undertreated ADHD. Children with ADHD and co-occurring conditions are well served by primary care physicians working within a multidisciplinary context, which may include developmental- behavioral or neurodevelopmental pediatricians, child and adolescent psychiatrists, child neurologists, psychologists, and therapists.

Evaluation

Children and adolescents with symptoms of inattention, hyperactivity, academic or social underachievement, or impulsivity should be evaluated first by a primary care physician, ideally one with whom the child has enjoyed continuity of care, rapport, and a strong therapeutic alliance. A complete evaluation of this nature is best accomplished with plenty of time for face-to-face review of records and a comprehensive history and physical examination; 90 to 120 minutes is a suggested minimum amount of time to do this effectively and correctly. Typically, it is necessary to schedule several appointments over the course of days or weeks.

History

The diagnostic evaluation of ADHD should begin with multiple informants (eg, caregiver[s], child, sibling[s]) giving a comprehensive medical history that includes details of the child’s problem behaviors, antecedents, and outcomes and consequences (Box 133.3). The physician should learn how these informants perceive and cope with the child’s behavioral problems and, in turn, how the child responds. Social/family stresses and the home and school environments should be described and evaluated and school reports and report cards reviewed. Interviewing the child alone provides an opportunity to better understand the child’s own thoughts, feelings, insight, judgment, self-image, and developmental status; however, children generally have poor insight into their ADHD symptoms and generally are not considered reliable informants for DSM-5 ADHD symptoms. Interviewing caregivers alone and talking with teachers by telephone before or after the visit can be quite helpful and alleviate some of the burden on the child of what is often initially a problem-oriented discussion about him, her, or them. The physician should inquire about the child’s difficulties, developmental strengths and competencies, adaptive strategies, stress management skills, self-regulation, protective factors, and adjustment. Other important information includes developmental history (and for older children academic history, which might include school report cards or other formal assessments), family history, and sleep and diet history.

The history should cover all DSM-5 criteria (Box 133.1). Parents/ caregivers and teachers may report the child’s behaviors using an ADHD-specific questionnaire or rating scale (eg, National Institute for Children’s Health Quality [NICHQ] Vanderbilt Assessment Scales), which can be found in the American Academy of Pediatrics (AAP) publication Caring for Children with ADHD: A Resource Toolkit for Clinicians. Non–ADHD-specific developmental screening tools do not replace this type of comprehensive ADHD assessment because their sensitivity and specificity for ADHD are inadequate. For younger children (aged 4–7 years), few validated screening tools exist (eg, Conners Comprehensive Behavior Rating Scales, ADHD Rating Scale-IV). Questionnaires can suggest a diagnosis but are insufficient to confirm a diagnosis; only clinical interview and observation can definitively confirm or rule out ADHD.

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