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Attention Deficit Hyperactivity Disorder

Susan L Smalley, University of California, Los Angeles, California, USA


Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders with onset in childhood. It is characterized by persistent problems of inattention, impulsivity and hyperactivity that result in impairment in social, academic and family functioning.

Introductory article
Article Contents
. Introduction . Symptoms and Subtypes . Incidence . Learning Disabilities and Co-morbidity Conditions . Aetiology . Treatment

Introduction
Attention decithyperactivity disorder (ADHD) is one of the most common psychiatric disorders with onset in childhood. It is characterized by persistent problems of inattention, impulsivity and hyperactivity that result in impairment in social, academic and family functioning. It is a highly heritable condition with genetic inuences accounting for 7090% of the susceptibility to ADHD. Co-morbid psychiatric disorders and learning disabilities are very common, occurring in 6070% of children and adolescents with ADHD. Treatment includes pharmacological and psychosocial interventions, which are extremely eective, leading to improvement in 8090% of cases.

Symptoms and Subtypes


Attention decithyperactivity disorder (ADHD) is a common behavioural disorder characterized by inattention, impulsivity and hyperactivity. Under the American Psychiatric Associations Diagnostic and Statistical Manual (DSM-IV) criteria, ADHD is diagnosed when symptoms of inattention and/or hyperactivity and impulsivity occur in at least two settings, lead to impairment in school, home or social activities, and have an onset prior to 7 years of age. Symptoms of inattention include failure to attend to details, diculty in sustaining attention, diculty in organizing tasks, poor listening, poor following through on tasks, forgetfulness, distractibility, losing things, and avoiding tasks requiring sustained mental eort. Symptoms of hyperactivity and impulsivity include dgeting, diculty in remaining seated, diculty in playing quietly, running about, being always on the go, excessive talking, blurting out answers, interrupting, and diculty in awaiting turns. Under DSM-IV, a child must have at least six of either inattentive or hyperactive/impulsive symptoms, impairment in at least two settings, and some symptom onset prior to age 7 years to meet criteria for ADHD. Three ADHD subtypes are recognized under the DSM system, based on the number of inattentive and hyper-

active/impulsive symptoms present. A child with six or more inattentive symptoms but fewer than six hyperactive/ impulsive symptoms receives a diagnosis of predominantly inattentive (AD) subtype, while the reverse symptom pattern yields a diagnosis of predominantly hyperactive (HI) subtype. The presence of numerous symptoms (  6) along both dimensions yields a diagnosis of combined type (CT), the subtype most consistent with the previous DSM classication schema of ADHD (i.e. DSM-IIIR). Under the International Classication of Diseases (ICD-10) criteria published by the World Health Organization, the same behavioural symptoms are classied as hyperkinetic disorder (HKD). Under this classication system, symptoms of hyperactive and impulsive behaviours are considered separately (not as a single domain as in DSM-IV) and symptoms across all three domains (at least six inattentive, at least three hyperactive, and at least one impulsive) are required for a diagnosis. In contrast to ADHD, two subtypes of HKD are recognized based on the presence or absence of conduct disorder, while the presence of depression or anxiety disorders is sucient to rule out a diagnosis of HKD. In contrast, co-morbid psychiatric disorders are diagnosed in the presence of ADHD but not used in subtype classication under the DSM system. While ADHD and HKD overlap in the core symptoms, criteria required for a diagnosis and recommendations for handling co-morbid psychiatric conditions result in somewhat dierent populations of aected individuals. The majority of research summarized in this article is based on subjects diagnosed using DSM criteria, generally samples diagnosed using DSM-IIIR, or more recently, DSM-IV. ADHD is a condition with onset in childhood that persists into adulthood in 3060% of cases. However, symptom presentation varies throughout the lifespan. In the preschool period, symptoms of hyperactivity often predominate, while inattentive symptoms may become more pronounced in adolescence as academic performance places greater demands on planning and organization. Although ADHD persists into adulthood, the symptom presentation and validity of using child-based diagnostic criteria in this age group are tenuous and currently areas of active research investigation.

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Attention Decit Hyperactivity Disorder

Incidence
ADHD is one of the most common behavioural disorders in children and adolescents, ranging from about 5% to 10% of the general population. Prevalence varies across studies as a function of changing diagnostic criteria, populations studied, and diagnostic instruments used. Prevalence rates based on assessments using a single instrument (e.g. teacher rating) and a single point in time range from 10% to 20%, while prevalence rates using DSM-IV, multiple informants, and direct clinical evaluations are on the order of 5% to 10%. Prevalence rates based on DSM-IV are somewhat higher than the 36% estimated using DSM-IIIR. The more narrowly dened HKD ranges in prevalence from 1% to 4%, reecting the exclusion of cases with co-morbid anxiety and depression and the AD subtype. Estimates of prevalence are generally based on school-age children and do not include preschool, late adolescent and adult populations. The increase in prevalence of ADHD under DSM-IV criteria compared with DSM-IIIR is largely due to the inclusion of the AD subtype in the current denition. The distribution of subtypes among ADHD school-age children is about 50% AD, 20% HI and 30% CT, again highlighting the importance of the AD subtype in dening the prevalence of this condition. Boys are more commonly aected with ADHD than girls, with gender ratios of 4:1 in epidemiological samples and 9:1 in clinic-based samples. Girls are more often diagnosed with the AD subtype, with the gender ratio based on epidemiological studies being 2:1 for this subtype compared to 4:1 for subtypes including hyperactive/ impulsive symptoms.

AD subtypes and not the HI subtype which, by denition, has few, if any, symptoms of inattention. Why ADHD and learning disabilities co-occur is an area of intense investigation. Family and twin studies yield mixed ndings regarding whether ADHD and learning disabilities, particularly reading disabilities, share common genetic underpinnings or are independently transmitted. As specic susceptibility genes underlying learning disability and ADHD are uncovered, the cause of the observed association will be indicated. Neuropsychological test performance suggests that ADHD results from decits in frontal lobe functioning reected by poor performance on tasks requiring planning and execution, known as executive function tasks. Poor working memory and poor performance on response inhibition tasks are also observed. However, no task or set of tests has shown a specicity or sensitivity to ADHD sucient to warrant use as a diagnostic test. In addition to learning disabilities, co-morbid psychiatric disorders are very common in ADHD aecting 60 70% of children and adolescents referred for clinical evaluation. The most common co-morbid conditions include conduct and oppositional deant disorder (30 50%), anxiety disorders (25%), mood disorders (1575%) and Tourette syndrome or chronic tics (734%). While psychiatric conditions occur in all three subtypes, conduct and oppositional disorders appear to be more common among the CT and HI subtypes while anxiety and mood disorders appear to be more common among the AD subtype.

Aetiology
The cause of ADHD is unknown. Although ADHD is a categorical diagnosis, it may be thought of as an extreme along a continuously distributed dimension of liability. Several dimensional measures of attention, hyperactivity and impulsivity are available and useful in the diagnosis of ADHD, reecting this continuum concept of ADHD. The conceptualization of ADHD as an extreme along a normal continuum is similar to the categorical diagnosis of mental retardation as an extreme along a dimension of IQ, or diabetes as an extreme along a continuum of glucose tolerance. Family, twin and adoption studies suggest that multiple genetic and environmental inuences acting in an additive fashion probably account for this continuous nature of liability to ADHD. ADHD is a highly familial disorder, i.e. it clusters in families. The frequency of ADHD is about ve- to sixfold greater among rst-degree relatives than in the general population. The frequency of ADHD in siblings of an ADHD child is about 25%, while the frequency among parents is 1220%. The rate of ADHD observed in parents may be underestimated owing to the diculty in diagnos-

Learning Disabilities and Co-morbidity Conditions


Academic failure, underachievement and poor school performance are common among children with ADHD. Determination of the extent to which poor academic performance results from diculties in attending, high activity level, or the presence of a co-morbid learning disability requires careful assessment of academic and intellectual functioning. Learning disabilities, particularly in reading, spelling and language-related areas, are very common in ADHD. Estimates range from 10% to 92%, largely owing to the wide variation in methods used to dene a learning disability. When a discrepancy score is used that takes into account the childs intellectual level (as assessed by IQ) and academic achievement, about 1538% of ADHD children have a co-morbid learning disability. Recent studies of ADHD subtypes suggest that the learning disabilities may be elevated only in the CT and
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Attention Decit Hyperactivity Disorder

ing ADHD from retrospective data and the questionable validity of using childhood criteria in diagnosing ADHD in adults. Rates of ADHD in second-degree relatives may be underestimated as well because studies have relied on family history data to determine aection status among such relatives, a method that is known to be less sensitive than direct interviews. However, using family history data, the frequency of ADHD in second-degree relatives is about twofold greater than that found among controls, again supporting the familial and likely genetic basis to ADHD. When patterns of ADHD in families are rigorously tested to evaluate underlying genetic models, multiple genes acting together in an additive fashion are indicated, although a single gene of moderate eect may be present as well. Familial clustering can result from shared environment and/or genetic factors. Twin and adoption studies are useful in disentangling genetic from shared environmental factors contributing to familial clustering. There are only a few adoption studies of ADHD, but these support a role of genes in this condition. There are over 10 twin studies including over 4000 twin pairs in which monozygotic and dizygotic twin similarity are examined on either the categorical diagnosis, ADHD, or dimensional measures of attention, hyperactivity and impulsivity. Using clinical or dimensional measures, twin data strongly support a major role of genes in the aetiology of ADHD, with estimates of heritability (the proportion of liability due to genetic dierences) of 7090%. Estimates vary as a function of the measures used, diagnostic criteria applied, ascertainment and samples studied, as well as variation in informants used in data collection (teacher versus parent); nevertheless, the data overwhelmingly support a major role of genetic inuences in the aetiology of ADHD. ADHD is probably a heterogeneous disorder, with many dierent genetic and environmental factors contributing to its aetiology. While specic rare conditions, such as generalized resistance to thyroid hormone, fragile X, tuberous sclerosis, low birth weight and fetal alcohol syndrome are associated with ADHD, the vast majority of cases of ADHD occur in the absence of any specic condition. Clinical heterogeneity is evident in ADHD as reected by the presence of subtypes and the high rates of co-morbidity of ADHD with other psychiatric disorders. Whether this clinical variability reects dierent underlying genetic or environmental risk factors is as yet unknown. Family and twin studies provide a useful tool in identifying whether clinical dierences reect aetiological subtypes. When relatives of ADHD individuals are examined for psychiatric disorders co-occurring with ADHD such as mood, anxiety and conduct/oppositional disorders, patterns emerge that suggest aetiological dierences may be present. For example, conduct disorders are signicantly increased among relatives of ADHD individuals with conduct disorders compared to relatives of

ADHD individuals without conduct disorders. Furthermore, among aected relatives, ADHD and conduct disorders occur together more often than expected by chance. These ndings suggest that ADHD with conduct disorders may represent a specic familial or genetic subtype of ADHD. A similar type of analysis with respect to anxiety disorders suggests that the co-morbidity of anxiety and ADHD does not represent a specic subtype but rather the joint occurrence of dierent genetic or shared environmental factors. Lastly, the co-morbidity of mood disorders and ADHD appears to be due to shared genetic or family risk factors. While family studies can suggest aetiological distinctions within ADHD, identication of underlying genes will ultimately clarify the relationship of clinical and aetiological heterogeneity. Another powerful approach to understanding the cause of ADHD has been the study of brain function, either indirectly through neuropsychological test performance, or more directly through neuroimaging technology, such as evoked related potentials (ERP), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and functional magnetic resonance imaging (MRI). The generally poor performance on executive function, working memory and response inhibition tasks suggests abnormalities in frontostriatal circuitry. MRI-based anatomical measures of prefrontal cortex and basal ganglia in ADHD suggest that dierences in such structures may underlie the observed decits. More direct studies of brain function come from ERP, SPECT and PET studies. From ERP and SPECT, underactive dorsolateral and anterior cingulate structures and striatal/frontal structures are indicated, respectively. Using cerebral glucose metabolism as a measure in a PET study, the left anterior frontal cortex was found to be less active among ADHD adults than normal adults. The result was less strong among ADHD adolescents. Future studies including functional brain research coupled with molecular genetic investigations are likely to yield the specic gene brainbehaviour pathways in ADHD. Genetic investigations of ADHD use powerful molecular methods to identify underlying susceptibility genes. Investigations of genes involved in dopamine regulation have ourished because of the recognized ecacy of drugs that eect dopamine regulation in the treatment of ADHD. Several genes involved in dopamine regulation, a dopamine transporter gene (DAT), and two dopamine receptors (D2 and D4) are suggested to play a role in ADHD. Replication studies of initial reports are under way, with positive replications reported for a dopamine receptor (D4) and DAT, at present, although negative ndings have also been reported. Many candidate gene investigations are being undertaken as well as systematic genomic scans to uncover susceptibility genes in ADHD.

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Attention Decit Hyperactivity Disorder

Treatment
Appropriate treatment requires an accurate diagnosis of ADHD. As no physiological or cognitive test is pathognomonic of ADHD, the diagnosis is based on behavioural symptoms. Evaluation of ADHD must include collection of information regarding the child or adolescent from multiple sources including parents, teachers and the child. Teacher questionnaires are useful for collecting information regarding the childs behaviour in the classroom. An interview with parents regarding developmental, neurological, medical, family and psychosocial history as well as the childs behaviour at home and with peers is needed. Because of the high rate of co-morbidity in ADHD, the diagnostic work-up must include a careful evaluation of potential co-morbid disorders including anxiety, depression and conduct/oppositional behaviour. A direct interview with the child/adolescent (depending on the childs age) is likely to reveal internalizing conditions (anxiety/ depression) that may not be reported by parents or teachers. A physical evaluation is needed to rule out neurological or organic syndromes that can mimic or cooccur with ADHD. A systematic evaluation for learning disabilities in which intellectual level and academic achievement are obtained will identify specic cognitive decits that may impact on academic performance and lead to or exacerbate ADHD symptomatology. Additional testing may be needed depending on specic areas of academic diculty or signs of motor, speech, hearing or other decits. Once the diagnosis of ADHD is made, a multimodal treatment approach is generally recommended; large-scale studies evaluating the ecacy of multimodal treatment are taking place in the United States and Europe. The two primary interventions are pharmacological and psychosocial treatments (such as behavioural intervention in the classroom or parent training). First-line medications are the stimulants such as dextroamphetamine (Dexedrine) or methylphenidate (Ritalin). The ecacy of stimulant medication in the treatment of ADHD is well known, with about 75% of children and adolescents responding to the rst trial and 8090% of children and adolescents responding to at least one stimulant medication. Stimulants also prove eective in treating ADHD in adults, although the response rate may be less than that observed in children and adolescents. Stimulant medications generally lead to improvement in classroom behaviour, academic performance and productivity; however, peer relations and social interactions also improve, indicating the importance of the use of stimulants during non-school activities as well. The side-eects of stimulant medication, if any, are decreased appetite, stomach ache, irritability and headaches. While reduced growth has been suggested as a consequence of stimulant usage, systematic investigations of this potential problem nd only minor growth

eects, and only in a small population of children receiving stimulants. Other than stimulants, tricyclic antidepressants prove eective in treating ADHD, although side-eects are of concern. The addition of serotonin uptake inhibitors such as uoxetine, sertraline, paroxetine and uvoxamine to the stimulant medication may be indicated if a co-morbid mood or anxiety disorder is present. The literature on the use of other medications alone or in combination with stimulants in the treatment of ADHD and co-morbid problems is sparse. Mood stabilizers provide little improvement of ADHD symptoms but may be useful if bipolar disorder is co-morbid. Alpha agonists may help in the treatment of associated aggressive behaviours and/or tics but do not lead to improvement of ADHD symptoms per se, and they may prove dangerous in combination with stimulant medications. Haloperidol or pimozide plus stimulants may prove useful in treating ADHD co-morbid with Tourette syndrome or chronic tics but are generally not used in the treatment of ADHD. Nonpharmacological interventions that have proved most eective in the treatment of ADHD include parent training for behavioural management and classroom interventions. Contingency management techniques at home and school, with close communication among teachers and parents, lead to substantial improvement in academic performance. Highly structured classrooms with contingency systems prove highly eective in improving academic performance and minimizing behavioural problems in ADHD. Individual psychotherapy can be eective in treating depression, anxiety, low self-esteem or other associated problems. Social skills training may be eective in children with ADHD, particularly in the estimated quarter who have what has been described as having a lack of social savoir-faire an inability to pick up or detect social cues. Psychosocial treatment in the absence of pharmacological intervention is eective in some cases, but the overall ecacy is less than that of the stimulants. Once susceptibility genes underlying ADHD are identied and their function in the brain is elucidated, behavioural and pharmacological interventions may be better tailored to the individuals genetic make-up, leading to improved ecacy of interventions alone or in combination. Currently, treatment is very eective in ADHD with 8090% of cases responding to stimulant intervention and additional psychosocial treatment leading to improvements in academic and social functioning.

Further Reading
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association.

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Attention Decit Hyperactivity Disorder

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