Attention Deficit Hyperactivity Disorder

1. Attention Deficit Hyperactivity Disorder James H. Johnson, Ph.D., ABPP University of Florida

2. ADHD: Nature of the Problem • ADHD is a neurodevelopmental disorder of childhood that is characterized by developmentally inappropriate levels of: • Hyperactivity, • Impulsivity, • Inattention.

3. ADHD: How Common is it? • Prevalence is estimated at 3 to 9 per cent of the elementary school population. • ADHD occurs more often in males than females, with the sex ratio being about 4 to 1 to 9 to 1. • It is one of the most common disorders of childhood • Accounts for a large number of referrals to pediatricians, family physicians and child mental health professionals.

4. ADHD: Not a New Problem • Characteristics of this disorder have been recognized for at least a century. • The disorder has been referred to by a variety of labels; • Minimal Brain Dysfunction (MBD) • Hyperkinetic Reaction of Childhood • Attention Deficit Disorder (ADD) • Attention Deficit Hyperactivity Disorder (ADHD)

5. ADHD: Evolution of the Disorder • Still (1902): ADHD Case study • Encephalitis epidemic of 1917 • Frontal lobe ablation studies with primates (1930’s) • Strauss’ work on Minimal Brain Dysfunction (1940's -1950's) • Beginnings of child psychopharmacology; Using Amphetamines for treatment – 1930-1940. • MBD becomes Hyperkinetic Disorder (the 1960’s)

6. ADHD: Evolution of the Disorder (cont.) • Hyperkinesis becomes ADD – The decade of the 70’s • Focus on Dietary Factors – Feingold and the 1970’s • Studies of psychophysiological responses of hyperactive children – the 1970’s • Development of objective diagnostic criteria: DSM III • Recognition of Attention Deficit Disorder – The early 80’s

7. ADHD: Evolution of the Disorder (cont.) • The decade of the 80’s: DSM III & DSM III-R stimulates ADHD research and the development of new assessment methods – new treatment methods - increased focus on biological factors. • The 1990’s - Present: Neuroimaging, genetics and and a reevaluation of DSM.

8. ADHD: Core Features • As noted earlier, ADHD is a disorder characterized by developmentally inappropriate levels of : • Hyperactivity, • Impulsivity, • Inattention.

9. DSM IV Symptoms of Hyperactivity • Often fidgets with hands or feet, squirms in seat. • Often leaves seat in classroom or in other situations in which remaining seated is expected • Often runs about or climbs excessively in situations in which it is inappropriate. • Often has difficulty playing or engaging in leisure activities quietly.

10. Hyperactive Symptoms • Is often "on the go" or often acts as if "driven by a motor“. • Often talks excessively when inappropriate to the situation • A combined total of 6 or more of hyperactivity/impulsivity criteria are required for diagnosis.

11. What do we Know about Hyperactivity? • Children with ADHD are more active, restless, and fidgety than normal children during the day and during sleep. • There are different types of hyperactivity. • Gross Motor Activity • Restless/Squirmy • Occasionally see verbal hyperactivity • Hyperactivity often varies according to situation. • Degree of hyperactivity may vary with age.

12. Symptoms of Impulsivity • Often blurts out answers before questions have been completed. • Often has difficulty awaiting turn. • Often interrupts or intrudes on others. Six symptoms of hyperactivity and impulsivity are required for diagnosis.

13. Symptoms of Inattention • Often fails to give close attention to details or makes careless mistakes. • Often has difficulties sustaining attention in tasks or play activities. • Often does not seem to listen when spoken to directly. • Often does not follow through on instructions and fails to finish homework, chores, or duties in the workplace

14. Symptoms of Inattention • Often has difficulty organizing tasks and activities • Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort. • Often loses things necessary for tasks or activities • Is often easily distracted by extraneous stimuli. • Is often forgetful in daily activities • (6 or more necessary for diagnosis)

15. What Do We Know About ADHD Attention Problems? • ADHD "attentional" problems may be most obvious on specific types of attentional tasks. • Children with ADHD seem to have their greatest difficulties with sustaining their attention in responding to tasks - in being vigilant. • Attention problems are usually seen most clearly in situations requiring the child to attend over time to dull, boring, and repetitive tasks.

16. Situational Variations in Symptoms • ADHD symptoms show significant variation across situations. • Children with ADHD do not display symptoms in all situations • The absence of symptoms in some situations does not mean that the child does not have ADHD.

17. Situations That Increase ADHD Symptoms • When the demands of the situation are to be good, to be still, and to be quiet. • The greater the demands, the more problematic the behavior of the child will likely become. • An exception might be in situations where the child is being continuously rewarded for complying with demands. • In familiar situations where novelty and task stimulation are low.

18. Other Situations That Increase Symptoms • Situations where there are low rates of intrinsic or external reinforcement. • When the child is fatigued. • Studies, monitoring 24 hour activity levels have suggested that the hours of 1 – 5 seem to be peak times for increased activity in children with ADHD.

19. Overview of Diagnostic Criteria • Symptom Criteria - Core Symptoms of Hyperactivity & Impulsivity and/or Inattention (Six or More Symptoms of either category). • Duration Criterion - Symptoms have Persisted for at Least 6 Months. • Developmental Criterion - Symptoms are Inconsistent with Developmental Level. • Impairment Criterion - Clear Evidence of Clinically Significant Impairment in Social, Academic, or Occupational Functioning

20. Overview of Criteria (cont.) • Age Criterion - Some Symptoms that Cause Impairment Were Present Before Age 7. • Situation Criterion - Some Impairment from Symptoms is Present in Two or More Settings. • NOTE. The failure to attend to full range of symptoms is not uncommon • Presence of hyperactivity, impulsivity, and inattention is not necessarily to be equated with ADHD.

21. Types of ADHD • Combined Type • Symptoms of hyperactivity, impulsivity and inattention. • Hyperactive/Impulsive • Symptoms of hyperactivity and impulsivity. • Predominately Inattentive • Symptoms of inattention.

22. ADHD Mimicry • Sensory Impairments • Medication side effects • Phenobarbital • Dilantin • Some Asthma Medications • Seizure Disorder • RTH (Resistance to Thyroid Hormone) • PTSD • Bipolar Disorder • Anxiety Disorders • Depressive Disorders

23. Comorbid Conditions • What are comorbid conditions? • Controversy over use of the term. • Why is it essential to consider the possibility of comorbid conditions in assessing children with ADHD? • Importance of distinguishing between comorbid conditions and mimicry. • What is the frequency of comorbidities in children with ADHD?

24. Comorbid Conditions • Learning Disabilities - 19 to 26% • Oppositional Defiant Disorder - 40% Conduct Disorder - 25% children; 45-50% Adolescents. • Anxiety Disorders - 30% • Depressive Disorder - 10 - 30% • Bipolar Disorder – up to 20%. • Tics and Tourette’s Disorder – 7% of children with ADHD have a tic disorder. • 40 to 50% of those with Tourette’s disorder have ADHD

25. Developmental Issues • There are factors in infancy, such as difficult temperament, that appear to be early precursors of ADHD. • Initial development of ADHD is most often during the preschool years. • While there is often a decline in the level of hyperactivity and some improvement in attention and impulse control in adolescence, perhaps 80 % continue to be impaired by their symptoms and meet current diagnostic criteria. • A significant number of children with ADHD (probably over 50%) continue to display problems into the adult years.

26. Prognosis of ADHD • Outcome of ADHD in adolescents is highlighted by the results of a study by Barkley, Fischer, et al, (1990). • This study followed a large sample of ADHD (158) and normal children (81) prospectively for 8 years after diagnosis. • 123 hyperactive children and 66 normals were located, interviewed and complete questionnaires. • In the hyperactive group 12 (9.7%) were female and 111 were male. In the normal group 4 of the subjects were female and 62 were male.

27. Prognosis In Adolescence • The vast majority of the hyperactive subjects (71.5%) met DSM III-R criteria for ADHD at follow up. • More than 59% met criteria for Oppositional Defiant Disorder as compared to 11% of the controls. •  Approximately 43 % of the hyperactive group could be diagnosed as CD as compared to 1.6% of the control group.

28. Prognosis Continued • Hyperactive subjects were more likely to have had an auto accident, to have had more automobile accidents, to have had more bodily injuries in accidents, and to be at fault for accidents more often than did controls. • Adolescents in the hyperactive group were also more likely to have received traffic citations, especially for speeding

29. Prognosis Continued • Cigarette and alcohol use were the only categories of substance use that differentiated hyperactives and normals. • When the the hyperactive sample was separated into groups (purely ADHD and ADHD + CD) purely ADHD subjects showed no greater use of cigarettes, alcohol, or marijuana than did normal controls. • Mixed hyperactive/Conduct disordered children displayed two to five times the rate of substance use as did pure hyperactives or normals.

30. Prognosis Continued • Three times as many hyperactives had failed a grade (29.3% versus 10%), had been suspended (46.3% versus 15.2%) or had been expelled (10.6% versus 1.5%). • Results indicated that hyperactivity alone increases the risk of suspension (30.6% vs 15.2%), and dropping out • (4.8% vs 0% ) as compared to controls • However, the added diagnosis of CD greatly increases the risk (67% suspended, 13% dropped out). • The presence of CD accounted almost entirely for the > risk of expulsion within the hyperactive group

31. Prognosis In Adulthood • As many as 67% of children diagnosed with ADHD will display symptoms in adulthood serious enough to interfere with academic, vocational or social functioning. • There are indications that the type of ADHD that persists into adulthood is more highly genetic than the type that remits in childhood. • ADHD in adults is sometimes considered a “hidden disorder” as symptoms are often obscured by other problems. • Prevalence is thought to be 2 – 4% with sex ratio of 2 – 1 or lower).

32. Risk Factors • Maternal cigarette use • Maternal alcohol use • Unusually long or short labor • Forceps delivery • Toxemia • Meconium staining • Birth during the month of September. • Minor physical anomalies

33. Etiology - Genetics • Between 10 and 35 per-cent of the immediate family members of children with ADHD also display this disorder. •  Risk for siblings of children with disorder is approximately 32% • If a parent has ADHD the risk to offspring is on the order of 50+% • Twin studies suggest concordance rates for monozygotic twins is around 80% with concordance rates of approximately 30% for dizygotic twins. • Overall, twin studies suggest an average heritability of .80

34. Etiology: Molecular Genetics • Molecular genetics has begun to identify specific genes related to ADHD. • A “dopamine type 2 gene” has been found to be related to ADHD as well as Tourette’s and alcoholism. • More recently a "dopamine transporter gene" and a “dopamine repeater gene”have been identified. • This gene, found to be related to ADHD in multiple studies, seems to be related to post-synaptic sensitivity in the frontal and prefrontal cortical regions and to be associated with executive functions.

35. Genetic Contributions (cont.) • With developments in molecular genetics occurring at an increasingly rapid rate (due to the Human Genome Project), in the near future, we may have genetic tests that can provide early screening for ADHD and possibly associated comorbidities. • Genetic factors are clearly strongly implicated in the development of this disorder. • Hereditary is one of the most well supported etiological factors in the development of ADHD

36. Etiology – Neurological Insult • Multiple factors that can result in brain damage are associated with ADHD. • For example, anoxia, is associated with increased frequencies of hyperactivity and attentional problems. • ADHD occurs more often in children with seizure disorders, who are presumed to have neurological involvement • As was noted earlier, diseases such as encephalitis can also result in symptoms of ADHD as can various types of infections.

37. Etiology: Brain Damage • These findings suggest that neurological insult can result in an increased probability of developing ADHD. • However, most children with ADHD do not have a significant history of brain injury. • Indeed, such injuries are unlikely to account for ADHD in most children. • In fact probably 95% of hyperactive children show no evidence of documentable neurological impairment. • This does not mean, however, that neurological factors are not involved.

38. Neuropsychological Test Findings • Results from research involving neuropsychological testing has often suggested that children with ADHD have problems; • in inhibiting behavioral responses, • with working memory, • with planning and organization, • with verbal fluency, • with perserveration, • In motor sequencing, • with other frontal lobe functions.

39. Research with Neuropsychological Testing (Cont.) • Not only do children with ADHD show executive functioning deficits but siblings of ADHD children who do not have ADHD, have milder yet significant impairments of the same type. • This suggests a possible genetic risk for executive function deficits in families.

40. Cerebral Blood Flow • Studies of cerebral blood flow in ADHD and normal children have consistently shown decreased blood flow to the prefrontal regions and pathways connecting these regions to the limbic system via the striatum and specifically its anterior region (the Caudate Nucleus) • Studies using PET scans to assess cerebral glucose metabolism in the frontal regions have found diminished metabolism in, adults and adolescent females with ADHD.

41. Cerebral Blood Flow Continued • Significant correlation's between diminished metabolic activity in the left anterior frontal region and severity of symptoms in adolescents with ADHD have also been demonstrated • This demonstration of a relationship between decreased metabolic activity of certain brain regions and severity of ADHD symptoms is crucial to documenting the importance of the link between brain activation and behaviors associated with ADHD

42. Frontal Lobes

43. Basal Ganglia

44. Striatal Network

45. MRI Studies • Early studies found differences in the Corpus Callosum, with this structure being smaller in children with ADHD. – Not always replicated. • Other MRI studies have found children with ADHD to have a smaller left caudate nucleus than did normal children. These findings are interesting in light of the results of earlier blood flow studies suggesting lower levels of activation in this specific area in children with ADHD.

46. MRI Continued • Several more recent MRI studies, with larger samples, have replicated these early results by finding that ADHD children had significantly smaller anterior right frontal regions, a smaller caudate nucleus, and smaller golbus pallidus regions that normals. • Research has also found decreased cerebellar volume in ADHD children. • Work in this area suggests that abnormalities in the development of the frontal-striatal regions may well underlie the development of ADHD.

47. Neurotransmitter Deficiencies • The possibility of a neurotransmitter dysfunction in children with ADHD has been suggested for many years. • This notion seemed to originate from observations of the response of children with ADHD to different type of stimulant drugs. • The fact that stimulant drugs have an impact on ADHD and that they increase dopamine has contributed to the neurotransmitter dysfunction hypothesis.

48. Neurotransmitter Deficiencies • There is more direct evidence of neurotransmitter deficiencies from studies of cerebral spinal fluid in ADHD and normal children which suggests decreased dopamine levels in ADHD children • There is also some evidence of a deficiency in the availability of norepinephrine in children with ADHD. • This is of interest given that a very new non-stimulant ADHD medication, Straterra, is thought to act on norepinephrine levels.

49. Etiology: Psychosocial Factors • There is little evidence for the role of psychosocial factors in the development of ADHD, although factors such as parent-child conflict may exacerbate problems in a child with ADHD. • Psychosocial factors may also contribute to the development of certain comorbid disorders that may complicate the clinical picture.

50. Etiology: Overview • In reviewing the literature on the etiology of ADHD, Barkley suggests … • “It should be evident from the research…that neurological and genetic factors make a substantial contribution to symptoms of ADHD and the occurrence of this disorder. • A variety of genetic and neurological etiologies (e.g., pregnancy and birth complications, acquired brain damage, toxins, infections, and genetic effects) can give rise to the disorder through some disturbance in a finalcommon pathway in the nervous system.