Attention-deficit hyperactivity disorder

			PET scans of glucose metabolism in the brains of a normal adult (left) compared to an adult diagnosed with ADHD (right).[22] "This PET scan was taken from Zametkin's landmark 1990 study, which found lower glucose metabolism, in the brains of patients with ADHD who had never taken medication. Scans were taken while patients were engaging in tasks requiring focused attention. The greatest deficits were found in the motor cortex and superior prefrontal cortex.

Attention-Deficit Hyperactivity Disorder (ADHD), or Hyperkinetic Disorder, is a neurobehavioural developmental disorder affecting about 5% of the world's population. It typically presents itself during childhood, and is characterized by a persistent pattern of inattention and/or hyperactivity, as well as forgetfulness, poor impulse control or impulsivity, and distractibility. ADHD is currently considered to be a persistent and chronic condition for which no medical cure is available. ADHD is most commonly diagnosed in children and, over the past decade, has been increasingly diagnosed in adults. About 60% of children diagnosed with ADHD retain the condition as adults. It appears to be highly heritable, although 1/5 of all cases are estimated to be caused from trauma or toxic exposure. Methods of treatment usually involve some combination of medications, behaviour modifications, life style changes, and counseling.

The scientific consensus in the field is that ADHD is a disorder which impairs functioning, and that many adverse life outcomes are associated with ADHD; however, there are diverse views within and outside the scientific community regarding its classification as a single syndrome, its causes, its treatment, and even the existence of ADHD. See Controversy about ADHD.

.Classification
ADHD is a developmental disorder, in that, in the diagnosed population, certain traits such as impulse control significantly lag in development when compared to the general population. Using magnetic resonance imaging, this developmental lag has been estimated to range between 3 years, to 5 years in the prefrontal cortex of those with ADHD patients in comparison to their peers; consequently these delayed attributes are considered an impairment. ADHD has also been classified as a behavior disorder and a neurological disorder or combinations of these classifications such as neurobehavioural or neurodevelopmental disorders.

Symptoms
The most common symptoms of ADHD are distractibility, difficulty with concentration and focus, short term memory slippage, procrastination, problems organizing ideas and belongings, tardiness, impulsivity, and weak planning and execution. Not all people with ADD have all the symptoms. Most ordinary people exhibit some of these behaviors but not to the point where they seriously interfere with the person's work, relationships, or studies or cause anxiety or depression. Children do not often have to deal with deadlines, organization issues, and long term planning so these types of symptoms often become evident only during adolescence or adulthood when life demands become greater. Hyperactivity is common among children with ADHD but tends to disappear during adulthood. However over half of children with ADHD continue to have symptoms of inattention throughout their lives.

Causes
According to a majority of medical research in the United States, as well as other countries, ADHD is today generally regarded as a chronic disorder for which there are some effective treatments, but no true cure. Evidence suggests that hyperactivity has a strong heritable component, and in all probability ADHD is a heterogeneous disorder, meaning that several causes could create very similar symptomology. Candidate genes include dopamine transporter (DAT), dopamine receptor D4 (DRD4), dopamine beta-hydroxylase (DBH), monoamine oxidase A (MAOA), catecholamine-methyl transferase (COMT), serotonin transporter promoter (SLC6A4), 5-hydroxytryptamine 2A receptor (5-HT2A), and 5-hydroxytryptamine 1B receptor (5-HT1B). Researchers believe that a large majority of ADHD arises from a combination of various genes, many of which affect dopamine transporters.Suspect genes include the 10-repeat allele of the DAT1 gene,[14] the 7-repeat allele of the DRD4 gene,and the dopamine beta hydroxylase gene (DBH TaqI).

Genome wide surveys have shown linkage between ADHD and loci on chromosomes 7, 11, 12, 15, 16, and 17. If anything, the broad selection of targets indicates the likelihood that ADHD does not follow the traditional model of a "genetic disease" and is better viewed as a complex interaction among genetic and environmental factors. As the authors of a review of the question have noted, "Although several genome-wide searches have identified chromosomal regions that are predicted to contain genes that contribute to ADHD susceptibility, to date no single gene with a major contribution to ADHD has been identified."Chromosomes disaffecting health or life expectancy are not expressed by everyone with the same DNA, and have only been found in combination with one or more other chromosomes. One reason for this may be that nature selects against genetic abnormalities that do not have any advantage.

Studies show that there is a familial transmission of the disorder which does not occur through adoptive relationships. Twin studies indicate that the disorder is highly heritable and that genetics contribute about three quarters of the total ADHD population. While the majority of ADHD is believed to be genetic in nature, roughly 1/5 of all ADHD cases are thought to be acquired after conception due to brain injury caused by either toxins or physical trauma prenatally or postnatally.

Additionally, SPECT scans found people with ADHD to have reduced blood circulation,and a significantly higher concentration of dopamine transporters in the striatum which is in charge of planning ahead. A study by the U.S. Department of Energy’s Brookhaven National Laboratory in collaboration with Mount Sinai School of Medicine in New York suggest that it is not the dopamine transporter levels that indicate ADHD, but the brain's ability to produce dopamine itself. The study was done by injecting 20 ADHD subjects and 25 control subjects with a radiotracer that attaches itself to dopamine transporters. The study found that it was not the transporter levels that indicated ADHD, but the dopamine itself. ADHD subjects showed lower levels of dopamine across the board. They speculated that since ADHD subjects had lower levels of dopamine to begin with, the number of transporters in the brain was not the telling factor. In support of this notion, plasma homovanillic acid, an index of dopamine levels, was found to be inversely related not only to childhood ADHD symptoms in adult psychiatric patients, but to "childhood learning problems" in healthy subjects as well.

Although there is evidence for dopamine abnormalities in ADHD, it is not clear whether abnormalities of the dopamine system are the molecular abnormality of ADHD or a secondary consequence of a problem elsewhere. Researchers have described a form of ADHD in which the abnormality appears to be sensory overstimulation resulting from a disorder of ion channels in the peripheral nervous system.

PET scans of glucose metabolism in the brains of a normal adult (left) compared to an adult diagnosed with ADHD (right)."This PET scan was taken from Zametkin's landmark 1990 study, which found lower glucose metabolism, in the brains of patients with ADHD who had never taken medication. Scans were taken while patients were engaging in tasks requiring focused attention. The greatest deficits were found in the motor cortex and superior prefrontal cortex."An early PET scan study found that global cerebral glucose metabolism was 8.1% lower in medication-naive adults who had been diagnosed as ADHD while children. The image on the left illustrates glucose metabolism in the brain of a 'normal' adult while doing an assigned auditory attention task; the image on the right illustrates the areas of activity in the brain of an adult who had been diagnosed with ADHD as a child when given that same task; these are not pictures of individual brains, which would contain substantial overlap, these are images constructed to illustrate group-level differences. Additionally, the regions with the greatest deficit of activity in the ADHD patients (relative to the controls) included the premotor cortex and the superior prefrontal cortex. A second study in adolescents failed to find statistically significant differences in global glucose metabolism between ADHD patients and controls, but did find statistically significant deficits in 6 specific regions of the brains of the ADHD patients (relative to the controls). Most notably, lower metabolic activity in one specific region of the left anterior frontal lobe was significantly inversely correlated with symptom severity.These findings strongly imply that lowered activity in specific regions of the brain, rather than a broad global deficit, is involved in ADHD symptoms. However, these readings are of subjects doing an assigned task. They could be found in ADHD diagnosed patients because they simply were not attending to the task. Hence the parts of the brain used by others doing the task would not show equal activity in the ADHD patients.

The estimated contribution of non genetic factors to the contribution of all cases of ADHD is 20 percent.The environmental factors implicated are common exposures and include alcohol, in utero tobacco smoke and lead exposure. Lead concentration below the Center for Disease Control's action level account for slightly more cases of ADHD than tobacco smoke (290 000 versus 270 000, in the USA, ages 4 to 15).Complications during pregnancy and birth—including premature birth—might also play a role. It has been observed that women who smoke while pregnant are more likely to have children with ADHD. This could be related to the fact that nicotine is known to cause hypoxia (lack of oxygen) in utero, but it could also be that ADHD women have more probabilities to smoke both in general and during pregnancy, being more likely to have children with ADHD due to genetic factors.

Head injuries can cause a person to present ADHD-like symptoms, possibly because of damage done to the patient's frontal lobes. Because these types of symptoms can be attributable to brain damage, the earliest designation for ADHD was "Minimal Brain Damage".

There is no compelling evidence that social factors alone can create ADHD. Many researchers believe that attachments and relationships with caregivers and other features of a child's environment have profound effects on attentional and self-regulatory capacities. It is noteworthy that a study of foster children found that an inordinate number of them had symptoms closely resembling ADHD.An editorial in a special edition of Clinical Psychology in 2004 stated that "our impression from spending time with young people, their families and indeed colleagues from other disciplines is that a medical diagnosis and medication is not enough. In our clinical experience, without exception, we are finding that the same conduct typically labelled ADHD is shown by children in the context of violence and abuse, impaired parental attachments and other experiences of emotional trauma." Furthermore, Complex Post Traumatic Stress Disorder can result in attention problems that can look like ADHD, as can Sensory Integration Disorders.

Despite the lack of evidence that nutrition causes ADHD, studies have found that malnutrition is correlated with attention deficits.

According to an advanced high-precision imaging study by researchers at the United States National Institutes of Health's National Institute of Mental Health, an actual delay in physical development in some brain structures, with a median value of three years, was observed in the brains of 223 ADHD patients beginning in elementary school, during the period when cortical thickening during childhood begins to change to thinning following puberty. The delay was most prominent in the frontal cortex and temporal cortex, which are believed responsible for the ability to control and focus thinking, attention and planning, suppress inappropriate actions and thoughts, remember things from moment to moment, and work for reward, all functions whose disturbance is associated with a diagnosis of ADHD; the region with the greatest average delay, the middle of the prefrontal cortex, lagged a full five years in development in the ADHD patients. In contrast, the motor cortex in the ADHD patients was seen to mature faster than normal, suggesting that both slower development of behavioral control and advanced motor development might both be required for the restlessness and fidgetiness that characterise an ADHD diagnosis. Aside from the delay, both groups showed a similar back-to-front development of brain maturation with different areas peaking in thickness at different times. This contrasts with the pattern of development seen in other disorders such as autism, where the peak of cortical thickening occurs much earlier than normal.

The same laboratory had previously found involvement of the "7-repeat" variant of the dopamine D4 receptor gene, which accounts for about 30 percent of the genetic risk for ADHD, in unusual thinness of the cortex of the right side of the brain; however, in contrast to other variants of the gene found in ADHD patients, the region normalized in thickness during the teen years in these children, coinciding with clinical improvement.

Complicating factors
Many studies point to synthetic preservatives and artificial coloring agents aggravating ADD & ADHD symptoms in those affected. Older studies were inconclusive quite possibly due to inadequate clinical methods of measuring offending behavior. Parental reports were more accurate indicators of the presence of additives than clinical tests. Several major studies show academic performance increased and disciplinary problems decreased in large non-ADD student populations when artificial ingredients, including artificial colors were eliminated from school food programs.

Diagnosis
Many of the symptoms of ADHD occur from time to to time in everyone. In those with ADHD the frequency of these symptoms occur frequently and impair regular life functioning typically at school or at work. Not only will they perform poorly in task oriented settings but they will also have difficulty with social functioning with their peers. No objective physical test exists to diagnose ADHD in a patient. As with many other psychiatric and medical disorders, the formal diagnosis is made by a qualified professional in the field based on a set number of criteria. In the USA these critera are laid down by the American Psychiatric Association in their Diagnostic and Statistical Manual of Mental Disorders (DSM-IV ), 4th edition. Based on the DSM-IV criteria listed below, three types of ADHD are classified:

1. ADHD, Combined Type: if both criteria 1A and 1B are met for the past 6 months
2. ADHD Predominantly Inattentive Type: if criterion 1A is met but criterion 1B is not met for the past six months
3. ADHD, Predominantly Hyperactive-Impulsive Type: if Criterion 1B is met but Criterion 1A is not met for the past six months.
The terminology of ADD expired with the revision of the most current version of the DSM. Consequently, ADHD is the current nomenclature used to describe the disorder as one distinct disorder which can manifest itself as being a primary deficit resulting in hyperactivity/impulsivity (ADHD, predominately hyperactive-impulsive type) or inattention (ADHD predominately inattentive type) or both (ADHD combined type).

DSM-IV criteria for ADHD
I. Either A or B:

A. Six or more of the following symptoms of inattention have been present for at least 6 months to a point that is disruptive and inappropriate for developmental level:
Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities.
Often has trouble keeping attention on tasks or play activities.
Often does not seem to listen when spoken to directly.
Often does not follow instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions).
Often has trouble organizing activities.
Often avoids, dislikes, or doesn't want to do things that take a lot of mental effort for a long period of time (such as schoolwork or homework).
Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools).
Is often easily distracted.
Often forgetful in daily activities.
B. Six or more of the following symptoms of hyperactivity-impulsivity have been present for at least 6 months to an extent that is disruptive and inappropriate for developmental level:
Often fidgets with hands or feet or squirms in seat.
Often gets up from seat when remaining in seat is expected.
Often runs about or climbs when and where it is not appropriate (adolescents or adults may feel very restless).
Often has trouble playing or enjoying leisure activities quietly.
Is often "on the go" or often acts as if "driven by a motor".
Often talks excessively.
Impulsiveness
Often blurts out answers before questions have been finished.
Often has trouble waiting one's turn.
Often interrupts or intrudes on others (e.g., butts into conversations or games).
II. Some symptoms that cause impairment were present before age 7 years.

III. Some impairment from the symptoms is present in two or more settings (e.g. at school/work and at home).

IV. There must be clear evidence of significant impairment in social, school, or work functioning.

V. The symptoms do not happen only during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder. The symptoms are not better accounted for by another mental disorder (e.g. Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder).

In the tenth edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) the symptoms of ADD are given the name "Hyperkinetic disorders". When a conduct disorder (as defined by ICD-10) is present, the condition is referred to as "Hyperkinetic conduct disorder". Otherwise the disorder is classified as "Disturbance of Activity and Attention", "Other Hyperkinetic Disorders" or "Hyperkinetic Disorders, Unspecified". The latter is sometimes referred to as, "Hyperkinetic Syndrome".

The American Academy of Pediatrics Clinical Practice Guideline for children with ADHD emphasizes that a reliable diagnosis is dependent upon the fulfillment of three criteria:

The use of explicit criteria for the diagnosis using the DSM-IV-TR.
The importance of obtaining information about the child’s symptoms in more than one setting.
The search for coexisting conditions that may make the diagnosis more difficult or complicate treatment planning.
The first criterion can be satisfied by using an ADHD-specific instrument such as the Conners' Rating Scale. The second criterion is best fulfilled by examining the individual's history. This history can be obtained from parents and teachers, or a patient's memory.The requirement that symptoms be present in more than one setting is very important because the problem may not be with the child, but instead with teachers or parents who are too demanding. The use of intelligence testing, psychological testing, and neuropsychological testing (to satisfy the third criterion) is essential in order to find or rule out other factors that might be causing or complicating the problems experienced by the patient.

The Centers for Disease Control and Prevention (CDC) state that a diagnosis of ADD should only be made by trained health care providers, as many of the symptoms may also be part of other conditions, such as bodily illness or other physiological disorders, such as hypothyroidism. It is not uncommon that physically and mentally nonpathological individuals exhibit at least some of the symptoms from time to time. Severity and pervasiveness of the symptoms leading to prominent functional impairment across different settings (school, work, social relationships) are major factors in a positive diagnosis.

Adults often continue to be impaired by ADD. Adults with ADD are diagnosed under the same criteria, including the stipulation that their symptoms must have been present prior to the age of seven. Adults face some of their greatest challenges in the areas of self-control and self-motivation, as well as executive functioning, usually having more symptoms of inattention and fewer of hyperactivity or impulsiveness than children do.

Common comorbid conditions are Oppositional Defiance Disorder (ODD). About 20% to 25% of children with ADD meet criteria for a learning disorder. Learning disorders are more common when there are inattention symptoms.

Treatment
Main article: Attention-deficit hyperactivity disorder treatments
Singularly, stimulant medication is the most effective and cost efficient method of treating ADHD. Over 200 controlled studies have shown that stimulant medication is an effective way to treat ADHD. Methods of treatment usually involve some combination of medications, behaviour modifications, life style changes, and counseling. Behavioral parent training, behavior therapy aimed at parents to help them understand ADHD has also shown short term benefits. Omega-3 fatty acids, zinc and magnesium may have benefits with regards to ADHD symptoms.

Comorbid disorders or substance abuse can make finding the proper diagnosis and the right overall treatment more costly and time-consuming. Psychosocial therapy is useful in treating some comorbid conditions.

Prognosis
A diagnosis of ADHD implies an impairment in life functioning. Many adverse life outcomes are associated with ADHD.

During the elementary years an ADHD student will have more difficulties with work completion, productivity, planning, remembering things needed for school, and meeting deadlines. Oppositional and socially aggressive behavior is seen in 40-70 percent of children at this age. Even ADHD kids with average to above average intelligence show "chronic and severe under achievement". Fully 46% of those with ADHD have been suspended and 11% expelled. Thirty seven percent of those with ADHD do not get a high school diploma even though many of them will receive special education services.The combined outcomes of the expulsion and dropout rates indicate that almost half of all ADHD students never finish highschool.Only five percent of those with ADHD will get a college degree compared to twenty seven percent of the general population. (US Census, 2003)

Epidemiology
ADHD's prevalence worldwide is estimated to be a bit over 5%, with most of the reported variability being due to methodological characteristics of studies. 10% of males, and (only) 4% of females have been diagnosed in the U.S. This apparent sex difference may reflect either a difference in susceptibility or that females with ADHD are less likely to be diagnosed than males.

History
The clinical definition of "ADHD" dates to the mid-twentieth century, when physicians developed a diagnosis for a set of conditions variously referred to as "minimal brain damage", "learning/behavioural disabilities" or "hyperactivity". Researchers speculate that earlier references to the condition as mentioned in the examples below, have been made throughout history.

HippocratesIn 493 BC, physician-scientist Hippocrates described a condition that seems to be compatible with what we now know as ADHD. He described patients who had "quickened responses to sensory experience, but also less tenaciousness because the soul moves on quickly to the next impression". Hippocrates attributed this condition to an "overbalance of fire over water”. His remedy for this "overbalance" was "barley rather than wheat bread, fish rather than meat, water drinks, and many natural and diverse physical activities."Shakespeare made reference to a "malady of attention", in King Henry VIII. In 1845, Dr. Heinrich Hoffmann (a German physician and poet who wrote books on medicine and psychiatry) became interested in writing for children when he couldn't find suitable materials to read to his 3-year-old son. The result was a book of poems, complete with illustrations, about children and their undesirable behaviours. "Die Geschichte vom Zappel-Philipp" (The Story of Fidgety Philip) in Der Struwwelpeter was a description of a little boy who could be interpreted as having attention deficit hyperactivity disorder, or as merely a moral fable to amuse young children and encourage them to behave properly.

In 1902, the English pediatrician George Still gave a series of lectures to the Royal College of Physicians in England, and described a condition which some have claimed is analogous to ADHD. Still described a group of children with significant behavioral problems, caused, he believed, by an innate hereditary dysfunction and not by poor child rearing or environment.

The 1918–1919 influenza pandemic left many survivors with encephalitis, affecting their neurological functions. Some of these exhibited immediate behavioral problems which may correspond to ADHD (although no diagnosis for such a disorder existed at the time). This caused many later commentators to believe that the condition was the result of injury rather than heredity. The concept of hyperactivity not being caused by brain damage was first described by Stella Chess as, ""Hyperactive Child Syndrome" in 1960. This caused a significant rift in the understanding of the disorder. Europeans saw hyperkinesis as unusual and often associated it with retardation, brain damage, and conduct disorders, and changes to the ICD were not made until 1994. In the USA by 1966, following observations that the condition existed without any objectively observed pathological disorder or injury, researchers changed the terminology from Minimal Brain Damage to Minimal Brain Dysfunction.

In 1937 a Dr. Bradley in Providence, RI reported that a group of children with behavioral problems improved after being treated with stimulant medication. In 1957 the stimulant methylphenidate (Ritalin) became available. In its various forms (Ritalin, Focalin, Concerta, Metadate, and Methylin), it remains one of the most widely prescribed medications for ADHD. Ritalin was first produced in 1950. Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications. The drug began to be used for ADHD in the 1960s and steadily rose in use. In 1975 Pemoline (Cylert) was approved by the FDA for use in the treatment of ADHD. While an effective agent for managing the symptoms, the development of liver failure in 14 cases over the next 27 years would result in the manufacturer withdrawing this medication from the market. New delivery systems for medications were invented in 1999 that eliminated the need for multiple doses across the day or taking medication at school. These new systems include pellets of medication coated with various time-release substances to permit medications to dissolve hourly across an 8–12 hour period (Medadate CD, Adderall XR, Focalin XR) and an osmotic pump that extrudes a liquid methylphenidate sludge across an 8–12 hour period after ingestion (Concerta). In 2003 – Atomoxetine (Strattera) received the first FDA approval for a nonstimulant drug to be used specifically for ADHD. In 2007 Lisdexamfetamine becomes the first prodrug to receive FDA approval for ADHD. The landmark study of 1999 – The largest study of treatment for ADHD in history – is published in the American Journal of Psychiatry. Known as the Multimodal Treatment Study of ADHD (MTA Study), it involved more than 570 children with ADHD at 6 sites in the United States and Canada randomly assigned to 4 treatment groups. Results generally showed that medication alone was more effective than psychosocial treatments alone, but that their combination was beneficial for some subsets of ADHD children beyond the improvement achieved only by medication. More than 40 studies have subsequently been published from this massive dataset.

Psychiatry first codified a condition called “hyperkinetic reaction of childhood” in 1968, displaying the psychoanalytical influences of that time. The name Attention Deficit Disorder (ADD) was first introduced in DSM-III, the 1980 edition. By 1987 – The DSM-IIIR was released changing the diagnosis to "Undifferentiated Attention Deficit Disorder." Further revisions to the DSM were made in 1994 – DSM-IV described three groupings within ADHD, which can be simplified as: mainly inattentive; mainly hyperactive-impulsive; and both in combination. During 1996, ADHD accounted for at least 40% of child psychiatry references.

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