Pathophysiology of Attention-Deficit/Hyperactivity Disorder
chapter 43, page 577-596. Lippincott, Williams, & Wilkins, Philadelphia, PA, Fifth edition, (2002)Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. Its impact on society is enormous in terms of its financial cost, stress to families, adverse academic and vocational outcomes, and negative effects on self-esteem (1). Children with ADHD are easily recognized in clinics, in schools, and in the home. Their inattention leads to daydreaming, distractibility, and difficulties in sustaining effort on a single task for a prolonged period. Their impulsivity makes them accident prone, creates problems with peers, and disrupts classrooms. Their hyperactivity, often manifest as fidgeting and excessive talking, is poorly tolerated in schools and is frustrating to parents, who can easily lose them in crowds and cannot get them to sleep at a reasonable hour. In their teenage years, symptoms of hyperactivity and impulsivity diminish, but in most cases the symptoms and impairments of ADHD persist. The teen with ADHD is at high risk of low self-esteem, poor peer relationships, conflict with parents, delinquency, smoking, and substance abuse (1).
The validity of diagnosing ADHD in adults has been a source of much controversy (2). Some investigators argue that most cases of ADHD remit by adulthood (3), a view that questions the validity of the diagnosis in adulthood. Others argue that the diagnosis of ADHD in adults is both reliable and valid (2). These investigators point to longitudinal studies of children with ADHD, studies of clinically referred adults, family-genetic studies, and psychopharmacologic studies. Longitudinal studies have found that as many as two thirds of children with ADHD have impairing ADHD symptoms as adults. Studies of clinically referred adults with retrospectively defined childhood-onset ADHD show them to have a pattern of psychosocial disability, psychiatric comorbidity, neuropsychological dysfunction, familial illness, and school failure that resemble the well known features of children with ADHD.
Throughout the life cycle, a key clinical feature observed in patients with ADHD is comorbidity with conduct, depressive, bipolar, and anxiety disorders (4,5). Although spurious comorbidity can result from referral and screening artifacts (5), these artifacts cannot explain the high levels of psychiatric comorbidity observed for ADHD (4). Notably, epidemiologic investigators find comorbidity in unselected general population samples (6,7), a finding that cannot be caused by the biases that inhere in clinical samples. Moreover, as we discuss later, family studies of comorbidity dispute the notion that artifacts cause comorbidity; instead, they assign a causal role to etiologic relationships among disorders.