PATHOPHYSIOLOGY OF ATTENTION- DEFICIT/HYPERACTIVITY DISORDER
STEPHEN V. FARONE JOSEPH BIEDERMAN
Attention-deficit/hyperactivity disorder (ADHD) is a child- hood-onset, clinically heterogeneous disorder of inatten- tion, 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 diffi- culties in sustaining effort on a single task for a prolonged period. Their impulsivity makes them accident prone, cre- ates problems with peers, and disrupts classrooms. Their hyperactivity, often manifest as fidgeting and excessive talk- ing, is poorly tolerated in schools and is frustrating to par- ents, 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, delin- quency, smoking, and substance abuse (1).
adults with retrospectively defined childhood-onset ADHD show them to have a pattern of psychosocial disability, psy- chiatric comorbidity, neuropsychological dysfunction, fa- milial 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, de- pressive, bipolar, and anxiety disorders (4,5). Although spu- rious 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. More- over, as we discuss later, family studies of comorbidity dis- pute the notion that artifacts cause comorbidity; instead, they assign a causal role to etiologic relationships among disorders.
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 longitudi- nal studies of children with ADHD, studies of clinically referred adults, family-genetic studies, and psychopharma- cologic 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
Stephen V. Farone: Pediatric Psychopharmacology Unit, Child Psychia- try Service, Massachusetts General Hospital; Harvard Medical School; Massa- chusetts Mental Health Center; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, Massachusetts.
Joseph Biederman: Pediatric Psychopharmacology Unit, Child Psychia- try Service, Massachusetts General Hospital; Harvard Medical School, Boston, Massachusetts.
Any pathophysiologic theory about ADHD must address the large pharmacotherapy literature about the disorder. The mainline treatments for ADHD are the stimulant med- ications methylphenidate, pemoline, and dextroampheta- mine. These compounds are safe and effective for treating ADHD in children, adolescents, and adults (8,9). In addi- tion, to improving ADHD’s core symptoms of inattentive- ness, hyperactivity, and impulsivity, stimulants also improve associated behaviors, including on-task behavior, academic performance, and social functioning in the home and at school. In adults, occupational and marital dysfunction tend to improve with stimulant treatment. There is little evidence of a differential response to methylphenidate, pemoline, and dextroamphetamine. The average response rate for each is 70%.
Stimulants enhance social skills at home and in school.