Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology (original) (raw)

Background

Attention deficit hyperactivity disorder (ADHD) is a developmental condition of inattention and distractibility, with or without accompanying hyperactivity. There are 3 basic forms of ADHD described in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) of the American Psychiatric Association: inattentive; hyperactive-impulsive; and combined. [1]

Diagnostic criteria (DSM-5)

According to DSM-5, the 3 types of attention deficit/hyperactivity disorder (ADHD) are (1) predominantly inattentive, (2) predominantly hyperactive/impulsive, and (3) combined. The specific criteria for attention-deficit/hyperactivity disorder are as follows: [1]

Inattentive

This must include at least 6 of the following symptoms of inattention that must have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

• Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities
• Often has difficulty sustaining attention in tasks or play activities
• Often does not seem to listen to what is being said
• Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)
• Often has difficulties organizing tasks and activities
• Often avoids or strongly dislikes tasks (such as schoolwork or homework) that require sustained mental effort
• Often loses things necessary for tasks or activities (school assignments, pencils, books, tools, or toys)
• Often is easily distracted by extraneous stimuli
• Often forgetful in daily activities

Hyperactivity/impulsivity

This must include at least 6 of the following symptoms of hyperactivity-impulsivity that must have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

• Fidgeting with or tapping hands or feet, squirming in seat
• Leaving seat in classroom or in other situations in which remaining seated is expected
• Running about or climbing excessively in situations where this behavior is inappropriate (in adolescents or adults, this may be limited to subjective feelings of restlessness)
• Difficulty playing or engaging in leisure activities quietly
• Unable to be or uncomfortable being still for extended periods of time (may be experienced by others as “on the go” or difficult to keep up with)
• Excessive talking
• Blurting out answers to questions before the questions have been completed
• Difficulty waiting in lines or awaiting turn in games or group situations
• Interrupting or intruding on others (for adolescents and adults, may intrude into or take over what others are doing)

Other

• Onset is no later than age 12 years
• Symptoms must be present in 2 or more situations, such as school, work, or home
• The disturbance causes clinically significant distress or impairment in social, academic, or occupational functioning
• Disorder does not occur exclusively during the course of schizophrenia or other psychotic disorder and is not better accounted for by mood, anxiety, dissociative, personality disorder or substance intoxication or withdrawal

In addition, attention-deficit/hyperactivity disorder is specified by the severity based on social or occupational functional impairment: mild (minor impairment), moderate (impairment between “mild” and “severe”), severe (symptoms in excess of those required to meet diagnosis; marked impairment).

Case study

The parents of a 7-year-old boy take him to the family practitioner because they have become increasingly concerned about his behavior not only in school but also a home. In the first grade, he has been bored, disruptive, fighting with classmates, and rude to his teacher. At home he cannot sit still and meals have been very unpleasant. The lad himself wonders why he is there. The parents have 2 older daughters who say their brother is a “pain” and spoiled. There were no pregnancy or birth problems and the child is on no medications. He has had all his scheduled shots.

The doctor decides more information is required before any treatment is indicated. She wants careful observations of the child both at home and in school. She wishes to talk with his teacher and suggests psychological testing. She also wants some time to see the patient alone. Careful investigation and thorough observations must be done before any intervention. Both the physician and the parents are concerned about overuse of medications and the value for behavioral interventions.

Pathophysiology

The pathology of ADHD is not clear. Psychostimulants (which facilitate dopamine release) and noradrenergic tricyclics used to treat this condition have led to speculation that certain brain areas related to attention are deficient in neural transmission. PET scan imaging indicates that methylphenidate acts to increase dopamine. [2] The neurotransmitters dopamine and norepinephrine have been associated with ADHD.

The underlying brain regions predominantly thought to be involved are frontal and prefrontal; the parietal lobe and cerebellum may also be involved. In one functional MRI study, children with ADHD who performed response-inhibition tasks were reported to have differing activation in frontostriatal areas compared with healthy controls. A 2010 study again indicated the presence of frontostriatal malfunctioning in the etiology of ADHD. [3] Although ADHD has been associated with structural and functional alterations in the frontostriatal circuitry, recent studies have further demonstrated changes just outside that region and more specifically in the cerebellum and the parietal lobes. [4] Another study using proton magnetic spectroscopy demonstrated right prefrontal neurochemical changes in adolescents with ADHD. [5]

Work by Sobel et al has demonstrated deformations in the basal ganglia nuclei (caudate, putamen, globus pallidus) in children with ADHD. The more prominent the deformations, the greater the severity of symptoms. Furthermore, Sobel et al have shown that stimulants may normalize the deformations. [6]

Adults with ADHD also have been reported to have deficits in anterior cingulate activation while performing similar tasks.

In a longitudinal analysis, Shaw et al used 389 neuroanatomic MRI images to compare 193 typically developing children with varying levels of symptoms of hyperactivity and impulsivity (measured with the Conners' Parent Rating Scale) with 197 children with ADHD (using 337 imaging scans). [7] Children with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning. This was most notable in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate. It was also noted in the orbitofrontal cortex and the right inferior frontal gyrus. Slower cortical thinning during adolescence is characteristic of ADHD and provides neurobiological evidence for dimensionality.

A PET scan study by Volkow et al revealed that in adults with ADHD, depressed dopamine activity in caudate and preliminary evidence in limbic regions was associated with inattention and enhanced reinforcing responses to intravenous methylphenidate. This concludes that dopamine dysfunction may be involved with symptoms of inattention but may also contribute to substance abuse comorbidity. [8]

Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses. [9]

According to a study of young children, there is evidence of early brain structural chages in pre-schoolers with ADHD. Researchers used high resolution anatomical (MPRAGE) images and cognitive and behavioral measures in a cohort of 90 medication-naïve preschoolers, aged 4–5 years (52 with ADHD, 38 controls; 64.4% boys). Results show reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children. The largest effect sizes were noted for right frontal and left temporal lobe volumes. Examination of frontal lobe sub-regions revelated that the largest between group effect sizes were evident in the left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. [10]

Narad et al. explored the relationship between traumatic brain injury (TBI) in children and development of secondary attention-deficit/hyperactivity disorder (SADHD). [11] They looked at concurrent cohort/prospective studies of children aged 3 to 7 years who were hospitalized overnight for TBI or orthopedic injury (OI; used as control group). A total of 187 children and adolescents were included in the analyses: 81 in the TBI group and 106 in the OI group. According to the results, early childhood TBI was associated with increased risk for SADHD. This finding supports the need for post-injury monitoring for attention problems. Consideration of factors that may interact with injury characteristics, such as family functioning, will be important in planning clinical follow-up of children with TBI.

Researchers in Denmark conducted a population-based cohort study to determine the association of prenatal exposure to antiepileptic drugs and risk of ADHD in offspring. Of more than 900,000 children, 580 were identified as having been exposed to valproate during pregnancy. Of them, 49 (8.4%) had ADHD. Among the children not exposed to the drug, approximately 30,000 (3.2%) had the disorder. This suggests that maternal use of valproate, but not other AEDs, during pregnancy is associated with an increased risk of ADHD in the offspring.

There has been concern about the association of maternal smoking during pregnancy and the development of ADHD in offspring. In a Finnish population-based study, researchers analyzed prenatal cotinine levels and offspring ADHD. Cotinine is a product formed after the chemical nicotine enters the body. Nicotine is a chemical found in tobacco products, including cigarettes and chewing tobacco. Measuring cotinine in people’s blood is the most reliable way to determine exposure to nicotine for both smokers and nonsmokers exposed to environmental tobacco smoke (ETS). Measuring cotinine is preferred to measuring nicotine because cotinine remains in the body longer. [12] The study measured maternal cotinine levels using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy. Results showed a dose-dependent relationship between nicotine exposure during pregnancy and offspring ADHD. [13]

Evidence of a neurobiologic contribution to the cause of ADHD continues to grow. A 12-year historical prospective nationwide cohort study examined whether adherence to methylphenidate (MPH) during early childhood predicts the initiation of antidepressants during adolescence. Researchers looked at children enrolled in an integrated care system who were first prescribed MPH between the ages of 6 and 8 years (N = 6830). They found that patients with higher adherence to MPH had a 50% higher risk (95% CI 1.16-1.93) of receiving antidepressants during adolescence when controlling for other comorbid psychiatric conditions and parental use of antidepressants. [14]

Epidemiology

Frequency

In 2016, an estimated 6.1 million US children aged 2–17 years (9.4%) were diagnosed with ADHD. Of these children, 5.4 million currently had ADHD, which was 89.4% of children ever diagnosed with ADHD and 8.4% of all U.S. children 2–17 years of age. Almost two-thirds of children with current ADHD (62.0%) were taking medication and slightly less than half (46.7%) had received behavioral treatment for ADHD in the past year; nearly one fourth (23.0%) had received neither treatment. [15]

According to a study by CDC researchers, more than 1 in 10 (11%) US school-aged children (4–17 years) had received an ADHD diagnosis by a health care provider by 2011, as reported by parents**.** A history of ADHD diagnosis by a health care provider increased by 42% between 2003 and 2011. [16]

A study by Akinbami and colleagues showed the following key findings: [17]

• From 1998–2000 through 2007–2009 - Percentage of children ever diagnosed with ADHD increased from 7–9%
• ADHD prevalence varies by race and ethnicity, with Mexican children having consistently lower prevalence compared with other racial or ethnic groups.
• From 1998 to 2009 - Prevalence of ADHD increased to 10% for children with family incomes less than 100% of the poverty level and to 11% for those with family income from 100-199% of the poverty level
• From 1998 to 2009 - Prevalence of ADHD rose to 10% in the midwestern and southern regions of the United States

In Great Britain, incidence is reported to be less than 1%. The differences between the US and British reported frequencies may be cultural ("environmental expectations") and due to the heterogeneity of ADHD (ie, the many etiological paths to get to inattention/distractibility/hyperactivity). Furthermore, the International Classification of Diseases, 10th Revision (ICD-10) criteria for ADHD used in Great Britain may be considered stricter than the DSM-5 criteria. However, other studies suggest that the worldwide prevalence of ADHD is between 8% and 12%.

Mortality/Morbidity

No clear correlation with mortality exists in ADHD. However, studies suggest that childhood ADHD is a risk factor for subsequent conduct and substance abuse problems, which can carry significant mortality and morbidity.

ADHD may lead to difficulties with academics or employment and social difficulties that can profoundly affect normal development. However, exact morbidity has not been established.

Sex

In children, ADHD is 3–5 times more common in boys than in girls. Some studies report an incidence ratio of as high as 5:1. The predominantly inattentive type of ADHD is found more commonly in girls than in boys.

In adults, the sex ratio is closer to even.

Age

In DSM-IV, the age of onset criteria was "some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years." This reflected the view that ADHD emerged relatively early in development and interfered with a child's functioning at a relatively young age. In DSM-5 this has been revised to "several inattentive or hyperactive-impulsive symptoms were present prior to 12 years." Thus, symptoms can now appear up to 5 years later. And, there is no longer the requirement that the symptoms create impairment by age 12, just that they are present. After childhood, symptoms may persist into adolescence and adulthood, or they may ameliorate or disappear.

The percentages in each group are not well established, but at least an estimated 15–20% of children with ADHD maintain the full diagnosis into adulthood. As many as 65% of these children will have ADHD or some residual symptoms of ADHD as adults.

The prevalence rate in adults has been estimated at 2–7%. The prevalence rate of ADHD in the adult general population is 4–5%. [18]

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Author

Stephen Soreff, MD President of Education Initiatives, Nottingham, NH; Faculty, Boston University, Boston, MA and Daniel Webster College, Nashua, NH

Stephen Soreff, MD is a member of the following medical societies: ACMHA: The College for Behavioral Health Leadership

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Glen L Xiong, MD Associate Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California, Davis, School of Medicine; Medical Director, Sacramento County Mental Health Treatment Center

Glen L Xiong, MD is a member of the following medical societies: AMDA - The Society for Post-Acute and Long-Term Care Medicine, American College of Physicians, American Psychiatric Association, Central California Psychiatric Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: SafelyYou, Blue Cross Blue Shield
book co-editor for: Wolter Kluwer, American Psychiatric Publishing Inc.