Indian Pediatrics 1998; 35:953-958 

Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is one of the commonest disorders in child psychiatry and affects between 3% and 6% of children with a preponderance of boys. It occurs in all cultures. The core symptoms are inattention, impulsiveness and hyperactivity. Children may show impairment in one of these areas or a combination of any. ADHD affects a child's ability to succeed at school and may persist into adulthood causing difficulties with later employment.

There has been a recent resurgence of interest in ADHD. This is probably related to the fact that the Revised Version of the American Psychiatric Association diagnostic system (DSM4-R)(1) has clarified the diagnosis and also because doctors have become much more comfortable at prescribing stimulant medication. Recent work has confirmed that medication is both effective and safe.

There has always been debate as to whether the cause of ADHD is primarily environmental (due to faulty parenting or deprivation) or whether it has a biological basis. Modern techniques are how starting to uncover underlying mechanisms in brain metabolism that indicate a biological basis for the disorder. It now seems most likely that. the main cause is biological with a strong genetic influence. It is however also probable that ADHD is precipitated in a biologically vulnerable brain exposed to adverse environmental influences.

Professionals have often argued that ApHD cannot be easily distinguished from conduct disorder. It has been shown how- ever that children presenting primarily with hyperactivity often make a later shift to conduct disorder. It seems very plausible that the conduct disorder is a result of the carer's reaction to the hyperactive behavior. It is also likely that the effect of the child's behavior on other children may lead to peer rejection and thus precipitate a conduct disorder in that unfortunate child.

This review will explore recent work published on ADHD and will provide guidance on the diagnosis and management of the disorder.

Diagnosis

The diagnosis of ADHD is based purely on symptoms. There are no physical signs or medical tests that will help although research particularly in the areas of molecular genetics and neuroimaging is ongoing. It is therefore often a rather subjective diagnosis but a vital factor is that those symptoms must be displayed in more than one environment-usually both at home and also at school. This criterion goes some way to avoiding criticism that a child with ADHD is simply "naughty". Most children with a mild conduct disorder show symptoms primarily at home but are well behaved at school. The diagnosis also specifies that the disorder must cause a significant impairment in daily life and this again excludes the child with mild, non-specific symptoms.

ADHD has been carefully defined both in the American Psychiatric Association Diagnostic and Statistical Manual (DSM- IV)(l) and the International Classification of Diseases (ICD-1O)(2). Rather confusingly the latter uses the tenninology Hyperkinetic Disorder (HKD) but in my experience the term ADHD is now used most frequently.

The diagnosis centres around three symptom domain groups-inattention, hyperactivity and impulsivity. These symptoms and the criteria for diagnosis are shown in summary form in Table I. It will be noted that DSM-IV recognize three main groups(a) those children showing significant problems in all three domains-the combined type; (b) those with symptoms mainly affecting attention the inattentive type; and (c) those children who are largely hyperactive or impulsive-the hyperactive/ impulsive type.

 

In addition to these diagnostic criteria there have been developed rating scales, which have purported to quantify the severity of the disorder. The non-quantitative Connors questionnaire(3) is also very useful to obtain a less subjective view of the child and are also helpful in tracking the effect of medication.

When making a diagnosis therefore the examiner will take a careful history from the parents concentrating on the points out-lined above and will also take evidence, if possible, from the school. In practice it is important to recognize that a child with ADHD may not show the diagnostic features in the consulting room, the unfamiliar environment often proving very successful in holding a child's attention.

Children with ADHD may obviously have other problems. A significant proportion (probably 20%) have specific learning difficulties, i.e., underlying cognitive function is normal but significant problems acquiring literacy or mathematical skills. ADHD may also be part of a child with generalized learning difficulties and it is often difficult to tease out the symptoms of ADHD from those behavioral symptoms associated with cognitive dysfunction. This exercise can be very fruitful however because these children often benefit from stimulant treatment.

It is also important to consider any underlying medical problems. Hypothyroidism rarely presents in this way, Un- diagnosed epilepsy, especially absence epilepsy, may cause confusion.

Epidemiology

Clearly, one of the major factors in the differing prevalence of ADHD is the confusion over definitions and certainly many surveys on prevalence have used differing criteria for diagnosis. However, those studies that have closely followed DSM criteria show a prevalence which varies between 5% and 10%(4), of the general population whereas those using ICD criteria (i.e., the full syndrome with limited co-morbidity) suggest a prevalence of around 1% to 2%(5).

It is also clear that the number of children presenting to professionals with this disorder is usually a lot less than the predicted prevalence from epidemiological studies. This may be due to factors such as cultural tolerance and differing expectations, i.e., some parent, schools and cultures will tolerate certain behaviors much better than others will who have high expectations of children's behavior. However, it is also true that with a more ready acceptance of the use of treatment such as medication, the presenting incidence of the disorder will rise.

Prognosis

Children with ADHD are at high risk of continuing problems into adolescence. Various long-term studies have shown a higher incidence of psychiatric disorder, antisocial behavior, criminality and drug abuse in adult life(6). They are also less likely to continue into further education and are more likely to be unemployed (Table II). They are also more likely to be involved in road traffic accidents.

Unfortunately, there are no studies that have shown that treatment with medication or behavior modification make any difference to the longer-term prognosis. Clearly this will also be dependent upon any underlying environmental or social factors. This is obviously an area for further research.

 

Etiology

The evidence for a biological cause for ADHD comes from neuroimaging including functional imaging, neurochemistry and also from molecular genetics.

Neuropsychological studies in ADHD point to a disorder of "executive functions". This is an exciting area of neuro-psychology that is helping to explain many disorders affecting higher brain function. Executive functions can be defined as "control processes involving inhibition and delay of responding allowing an individual to initiate, sustain, inhibit/stop, and shift."(7). It is thought that executive functions are controlled by the pre-frontal circuitry of the brain. Studies have, therefore, looked for abnormalities in these areas in children with ADHD.

Various neuroimaging techniques have been used and many studies have now shown fairly consistent abnormalities in the brain structure and function of children with ADHD. These techniques include MRI scans, functional MRI scans, positron-emission tomography (PET) and single photon emission tomography (SPECT). These abnormalities are largely right sided and reveal that many children with ADHD have a relatively small caudate nucleus, prefrontal region, globus pallidus and cerebellum. Functional studies have also shown relatively less activity in alI these areas. It has been estimated that overall there is a consistent reduction of 10% in these areas in children with ADHD compared with controls(8).
A pathophysiological model can then be constructed to formulate a hypothesis for the cause of ADHD(9). Executive functions are thought to be under the control of the cortical-striatal-thalamic-cortical circuit whereby the prefrontal cortex relays efferents to the caudate nucleus and subthalamic nucleus. Dopamine regulated circuits from the substantia nigra can influence this circuit. A' further dopamine system. relays inhibitory neural systems from the ventral tegmental area to the pre- frontal cortex.

Deficits in these dopamine-regulated circuits can then be improved by stimulants such as methylphenidate or dexamphetamine, which act, by slightly different mechanisms to .increase the synaptic concentration of dopamine.

There seems little doubt that ADHD has a strong genetic background(10). Studies have shown a higher than normal prevalence of ADHD in the parents of children with the disorder. Genetic studies have consistently shown a genetic component to ADHD with hereditability estimates ranging from 0.5 to 0.9. Twin studies have confirmed a much higher concordance rate for monozygotic compared to dizygotic twins and adoption studies have also confirmed a strong genetic component. The mode of inheritance however remains unclear.

Moletular genetic investigations have implicated the dopamine transporter gene (chromosome 5p 15.3) and the dopamine D4-receptor gene (chromosome 11p 15.5)(8). It is suggested that m ADHD there may be impairment of the mechanism for re-uptake of dopamine by the synapse (under the control of the dopamine transporter gene) and also altered sensitivity of the D4 receptor to synaptic dopamine (controlled by the D4 receptor gene). These investigations, although fascinating, must be seen as very preliminary findings.

Treatment

Stimulant medications (mainly methyl-phenidate and amphetamine) have been used for over 50 years and there is ample evidence of their effectiveness in treating ADHD. Overall, about 80% of children show some benefit and many children are transformed according to parents and teachers. These drugs appear to have few serious side effects(11).

The mode of action of stimulants is to block the dopamine and epinephrine transporters leading to an increase m synaptic concentration of monoamines producing an increased post-synaptic effect. The pharmacokinetics of the drugs leads to a peak action at about 1 hour and its disappearance after 3-4 hours. It is important to bear this short action in mind when managing treatment.

The usual practice would be to start treatment with methylphenidate 5 mg (1/2 tablet) given after breakfast once a day and after two weeks 5 mg around midday can be added if no side effects are seen. This twice a day dose is gradually increased until a satisfactory effect is seen. Most children respond to 10-15 mg twice a day. If necessary an additional (but usually smaller) dose may be given m the after- noon. If given after 4 p.m. however, it may interfere with sleep. There is a recommended maximum dose of 60 mg/ day but most children will respond to less than this. Dexamphetamine can be used m a similar fashion but the tablets consist of 5 mg only and the corresponding doses will therefore be half those of methylphenidate.

Side effects from these drugs tend to be relatively mild and uncommon. The most frequent side effect is' loss of appetite, which if severe may lead to loss of weight. If the treatment is given after meals this is less of a problem. High calorie drinks can be prescribed as a supplement to offset this problem. Headaches may occur and occasionally are severe enough that the treatment. has to be stopped. Insomnia. is a further side effect but is usually avoided by giving the last dose no later than 4 p.m. (or 4 hours before the child's bedtime); It is reported that children prone to tics (or even with Tourettes syndrome) may be made worse but this seems to be uncommon. Some parents describe their child as being irritable or moody and this may lead to withdrawal of the treatment. There has been concern m the past about impairment of growth but this has largely been discounted(12). Rare reports of hypertension and thrombocytopenia have occurred and some authorities recommend regular blood pressure and full blood count checks. Caution is also advised m children with epilepsy with some concern that stimulants may exacerbate fits.

Other drugs have been used with some benefit. The other stimulant, pemoline, has now been withdrawn because of concerns about hepatotoxicity. Tricyclic antidepressants, especially imipramine, may be helpful especially if given as an evening dose. Clonidine can be used again m the evening and is particularly helpful if insomnia is part of the symptomatology or results as a side effect of the stimulants.

Behavioral mterventions have also been used although their effectiveness is not as clearly documented as medication. Behavior modification implies targeting appropriate behaviors to increase by a reward system and inappropriate behavior to decrease by some form of punishment. Rewards for appropriate behavior could be simply praise or some simple token. Punishment must be in a non-judgemental and loving mileu and may take the form of a short "time out". Modification of the class- room environment is also necessary to try and avoid unnecessary distractions and if possible provide some individual attention. A very structured timetable and work programme is helpful.

In conclusion, ADHD is an important disorder of childhood. It should be recognized and treated appropriately to enable children suffering from the condition to achieve their potential. The latest research techniques appear not only to help elucidate brain mechanism underlying ADHD but also may help us to understand more widely brain function in childhood.
 

Peter Morrell,
Consultant Pediatrician,
South Cleveland Hospital,
Marton Road,
Middlesbrough TS4 3BW, England,
e-mail: [email protected]
 

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