Elsevier

The Lancet

Volume 366, Issue 9481, 16–22 July 2005, Pages 237-248
The Lancet

Seminar
Attention-deficit hyperactivity disorder

https://doi.org/10.1016/S0140-6736(05)66915-2Get rights and content

Summary

Attention-deficit hyperactivity disorder (ADHD) is a disorder of inattention, impulsivity, and hyperactivity that affects 8–12% of children worldwide. Although the rate of ADHD falls with age, at least half of children with the disorder will have impairing symptoms in adulthood. Twin, adoption, and molecular genetic studies show ADHD to be highly heritable, and other findings have recorded obstetric complications and psychosocial adversity as predisposing risk factors. Converging evidence from animal and human studies implicates the dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits in the pathophysiology of ADHD, and molecular imaging studies suggest that abnormalities of the dopamine transporter lead to impaired neurotransmission. Studies during the past decade have shown the safety and effectiveness of new non-stimulant drugs and long-acting formulations of methylphenidate and amfetamine. Other investigations have also clarified the appropriate role of targeted psychosocial treatments in the context of ongoing pharmacotherapy.

Section snippets

Epidemiology and diagnosis

ADHD affects 8–12% of children worldwide, and results in inattention, impulsivity, and hyperactivity.4 The controversy about how to diagnose ADHD is seen in the differences between US diagnostic criteria for the disorder, as defined by the Diagnostic and Statistical Manual of the American Psychiatric Association (4th edition; DSM-IV), and the European diagnostic criteria for hyperkinetic disorder (HKD), as defined by the International Classification of Diseases (10th edition; ICD-10). Both

Genetics of ADHD

Is ADHD merely the extreme of a healthy variation exacerbated by adverse environmental circumstances rather than a medical disorder with biological causes (panel 2)? For many decades, studies have shown that ADHD is transmitted in families.54, 55 According to twin and adoption studies, genes have a substantial role in the familial transmission of ADHD. Figure 156 shows heritability data from twin studies of the disorder or quantitative measures of its symptoms from Australia, Sweden, the UK,

Pathophysiology

The idea that dysregulation of dopamine and norepinephrine circuits underlies ADHD was initially suggested by the action of drugs for the disorder, which increase the synaptic availability of these neurotransmitters, and by animals showing that lesions in dopamine pathways create animal models of ADHD, as shown in developing rats101 and monkeys.102 As one of the most compelling animal models of ADHD, the spontaneously hypertensive rat (SHR)103 shows dopamine release abnormalities in subcortical

Treatment

For 40 years, the main treatments for ADHD (panel 3) have been the stimulant drugs, methylphenidate and amfetamine, which are believed to enhance neurotransmission of dopamine and norepinephrine.135 The stimulant pemoline is less commonly used because of its hepatotoxic effects. Non-stimulant treatment has also been used, but for many years reduced efficacy and occurrence of side-effects had restricted their use. The average effect size for stimulants (0·91 for immediate release and 0·95 for

Conclusions

ADHD has emerged from the 20th century with a large amount of scientific work investigating its validity and clarifying clinical controversies. The disorder is highly prevalent worldwide, is associated with substantial life impairments, and frequently persists into adulthood. Hypotheses about the cause of ADHD have evolved from simple one-cause theories to the view that it is a complex, multifactoral disorder caused by the confluence of many different types of risk factors (ie, genetic,

Search strategy and selection criteria

To identify studies relevant to this Seminar, we searched MEDLINE citations (from January, 1966, to July, 2004) using PubMed. References cited in these works were also reviewed to identify additional works not indexed by MEDLINE. We refer readers to review articles or book chapters for comprehensive overviews that are beyond the scope of this Seminar.

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