ADHD

(4-2-15)

ADHD History

(2-27-14)

A century plus of difficulty sitting still

“Descriptions of what we know know as ADHD date back more than 100 years” (Bradshaw, 2001, p. 94)

“in the 19th century a German physician described the cartoon character Zappel-Phillip (‘Fidgety Phil’) as a ‘child who twitched and ‘twittled’ back and forth on a chair, and was unable to sit still.” (Bradshaw, 2001, p. 94)

1902  Dr. Still and “defects in moral control”

1904 Meyer reported inattention and impulsivity problems following brain injury

1917-18  encephalitis epidemic

• Kahn & Cohen (1937) “organically driven”
• sequelae of von Economo’s encephalitis included hypokinetic symptoms of Parkinson’s disease in adults and hyperkinesia in children; a neurological role involving basal ganglia was assumed

1930 Strauss “the brain damaged child”

1937  Bradley, Benzedrine, and the “paradoxical quieting effect”

“It appears paradoxical that a drug known to be a stimulant should produce subdued behavior in half of the children. It should be borne in mind, however, that portions of the higher levels of the central nervous system have inhibition as their function, and that stimulation of these portions might indeed produce the clinical picture of reduced activity through increased voluntary control.”

(Barkley, 1937, p. 582)

1957  Laufer & Denhoff “Hyperkenetic Impulse Disorder”

1959  Knobloch & Passamanick “a continuum of reproductive causality”

1960’s  “Minimal Brain Damage (MBD) “Minimal Brain Dysfunction” (MBD); Lauretta Bender proposes “maturational lag”

1968 DSM-II “Hyperkinetic reaction of childhood (or adolescence)”

1970’s Faulty attention & inhibitory control

1980  DSM-III “Attention Deficit Disorder” (ADD)

1987  DSM-III-R “Attention-deficit Hyperactivity Disorder” (ADHD)

• CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder) founded in 1987

1994  DSM-IV “Attention-Deficit/Hyperactivity Disorder” (ADHD)

• 1999 initial NIMH MTA (Multimodal Treatment Study) results published

2000 DSM-IV-TR “Attention-Deficit/Hyperactivity Disorder” (ADHD) (onset of some symptoms prior age 7)

• predominantly intattentive type
• predominantly hyperactive/impulsive type
• combined type

2013 DSM 5 “Attention-Deficit/Hyperactivity Disorder (ADHD)”: subtypes remain the same with slight name change; some attention to adult presentation; change in age of onset criteria (prior age 12), continued controversy (just like death, taxes, and the sun coming up tomorrow morning)

• predominantly intattentive presentation
• predominantly hyperactive/impulsive presentation
• combined presentation

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Characteristics of ADHD

(4-2-15)

A History

Defining features: a persistent pattern of inattention, hyperactivity, impulsivity more frequent and severe than age and gender peers in similar circumstances

Diagnosis of ADHD

Prevalence: As in all things, influenced by criteria selection, operationalization, and method of assessment

• DSM 5 reports prevalence of approximately 5% in children and 2.5% in adults
• CDC analysis of 2003 National Survey of Children’s Health (NSCH) data indicated that in 2003 approximately 4.4 children aged 4 to 17 years were reported to have a history of ADHD diagnosis; 2.5 million (56%) were reported to be currently taking medication for this disorder
  • national prevalence male: 11.0%
  • national prevalence female: 4.4%
  • national prevalence total: 7.8% (95% confidence interval 7.4 to 8.1)
  • Onset: at least some symptoms appear before age 12 (DSM 5; previously 7 in DSM-IV)
  • Course: there is usually some attenuation of symptoms with increasing age, especially the overactivity; but some degree of symptoms and associated social and academic impairment continue in a majority of diagnosed cases.
• Children diagnosed with ADHD are at risk for involvement in substance use and antisocial activities as adolescents and young adults. ADHD appears to interact with conduct problems to increase risk of greater and more diverse substance use (Barkley, Fischer, Smallish, & Fletcher, 2004).
• Subtypes:
  • (DSM 5): ADHD, Combined Presentation
  • ADHD, Predominantly Inattentive Presentation
  • ADHD, Predominantly Hyperactive/Impulsive Presentation
• Gender: More frequent in males than females.
  • Sex ration more skewed in clinic than in population sample.
• Comorbidity: Approximately 50% of clinic populations of children diagnosed with ADHD also meet criteria for ODD.
  • DSM 5 notes a 50% comorbidity for ODD with ADHD combined presentation and 25% comorbidity for predominantly inattentive presentation
  • DSM 5 notes 25% comorbidity for Conduct Disorder with ADHD combined presentation
  • DSM 5 notes that: “Most children and adolescents with disruptive mood dysregulation disorder have symptoms that also meet criteria for ADHD; a lesser percentage of children with ADHD have symptoms that meet criteria for disruptive mood dysregulation disorder.” (p. 65)
• Other frequently comorbid disorders include: Mood Disorders, Anxiety Disorders, Learning Disorders, tic disorders, autism spectrum disorders, and Communication Disorders.
  • DSM 5 notes that “Specific learning disorder commonly co-occurs with ADHD.” (p. 65)
  • DSM 5 notes that major depressive disorder: “occurs in a minority of individuals with ADHD but more often than in the general population” (p. 65)
• Even in the absence of formal reading disabilities, children with ADHD may unexpected weaknesses in learning and recall new information (Cutting et al., 2003)
• At least 50% of children diagnosed with Tourette’s Disorder also meet criteria for a diagnosis of ADHD, but most children with ADHD do not meet criteria for Tourette’s. In children who show both problems, the onset of the ADHD typically precedes the onset of Tourette’s.
  • Tourette’s syndrome is a tic disorder that consists of both vocal and motor tics
  • Tourette’s syndrome is ofter associated in the public’s mind with coprolalia (obscene speech, “potty mouth”) but while this occurs, it is not terribly common in individuals with Tourette’s; vocal (grunts, throat clearing, clicks, etc.) tics are more common than verbal tics (meaningful remarks, words); embarrasing remarks are more common than coprolalia. When there are verbal aspects to Tourette’s syndrome, this does appear to represent a failure of inhibitory control within the CNS (we all know the words we are no suppose to use in public).
• In the past a diagnosis of a Pervasive Developmental Disorder precluded a concurrent diagnosis of ADHD (because comoribity was so high), in DSM 5 concurrent diagnoses of Autism Spectrum Disorder and ADHD are allowed
• The relationship between ADHD in youth and an adolescent/adult diagnosis of Bipolar Mood Disorder remains a topic of active investigation and some controversy. Most children with diagnosed ADHD do not go on to develop manic episodes and bipolar disorder, but a small subpopulation does. These cases may represent:
  • a) the early symptoms of bipolar disorder misdiagnosed as ADHD
  • b) the comorbid occurrence of two mental disorder, possibly due to shared risk factors or etiological influences
  • c) a unique variation of ADHD/Bipolar Disorder
  • a fluctuating course of ADHD symptoms and adjustment,
  • poor response to treatment with CNS stimulants, and
  • a strong family history of Bipolar Disorder are often seen
  • as risk factors for later comorbidity with manic-depressive illness
  • Hazell et al. (2003) found that manic symptoms in young males with ADHD predicted lower global functioning but not a diagnosis of Bipolar Disorder in early adulthood, casting some doubt on the link between manic symptoms in childhood and later bipolar disorder.
    • additionally–some, perhaps many, youth diagnosed with bipolar disorder do not appear to go on to manifest classical bipolar disorder (full manic or hypomanic episodes) as adult, raising further questions about the link the conditions
    • DSM 5 has attempted to address these issues by creation of a new diagnostic category: Disruptive Mood Dysregulation Disorder

Etiology

Treatment

Gender and ADHD

Biederman et al. (2002) studied 140 boys & 140 girls with ADHD and 120 boys and 122 girls without ADHD

ADHD in girls was characterized by the prototypical symptoms of the disorder (Inatt., Impul., & Hyperact.), comorbid psychopathology, social dysfunction, cognitive impairments, school failure, and adversity in family environment.

Overall the profile of psychiatric comorbidity for ADHD was similar in boys and girls

• The only significant gender-by-diagnosis interaction was for substance use disorders: ADHD was a stronger risk factor for substance use disorders in girls than in boys
  • this finding would support targeting substance abuse prevention programs to girls with ADHD
• The other -by-diagnosis interactions were not significant: the other gender differences between boys and girls with ADHD were the same as the gender differences observed for boys and girls without ADHD
  • ADHD in girls was more likely to be predominantly the inattentive type
  • less likely to be associated with a learning disability in reading or mathematics
  • less likely to be associated with problems in school or fewer spare-time activities

These differences in phenotypic presentation may help account for the difference in referral rates to clinics of boys and girls with ADHD

A significant discrepancy has been noted between the male to female ratio for clinic-referred (10 to 1) and community samples (3 to 1) of children with ADHD

Biederman, J., Mick, E., Faraone, S.V., Braaten, E., Doyle, A., Spencer, T., Wilens, T.E., Frazier, E., & Johnson, M.A. (2002)

Cutting, L.E., Koth, C.W., Mahone, E.M., & Denckla, M.B. (2003). Evidence for unexplained weaknesses in learning in children with Attention-Deficit/Hyperactivity Disorder without reading disabilities. Journal of Learning Disabilities, 36, 259-269.

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Diagnosis of ADHD

	5 symptoms required of 9	6 symptoms of 9	7 symptoms of 9
John 3 symptoms of ADHD	no	no	no
Fred 4 symptoms	no	no	no
Sam 4 symptoms	no	no	no
Jimmy 5 symptoms	yes	no	no
Jose 5 symptoms	yes	no	no
Winny 5 symptoms	yes	no	no
Jill 6 symptoms	yes	yes	no
Bob 6 symptoms	yes	yes	no
John 7 symptoms	yes	yes	yes
Ron 9 symptoms	yes	yes	yes

Symptom Overlap

At different thresholds

	5 of 9 Child A/Child B	6 of 9 Child A/Child B	7 of 9 Child A/Child B
1	A	A	A
2	A	A	A
3	A	A	A B
4	A	A B	A B
5	A B	A B	A B
6	B	A B	A B
7	B	B	A B
8	B	B	B
9	B	B	B

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Possible etiologies of ADHD

(10-31-13)

Neurological factor explanations

Brain Damage: structural damage due to harmful influence

• Brain injury, especially hypoxic/anoxic insults, have been associated with attention deficits and hyperactivity.
• ADHD symptoms appear to be over represented in children with a history of seizure disorders.
• However, recall that brain injury acts as a “nonspecific risk factor” in children, and ADHD symptoms are neither exceptionally common or uniquely associated with these injuries.
• Reviews have suggested that <5% of children diagnosed with ADHD have any hard neurological findings indicative of actual brain damage.
• Conclusion: minor contributor, explains only a few cases.

Delayed Brain Maturation: brain is “normal”, just developing slowly

• Immature social behavior, neuromaturational delay on neurological examinations, and similarity of deficits in attention, impulse control, and self-regulation to younger normal children have been interpreted as possibly indicating a developmental delay in CNS maturation.
• This position was more tenable when it was believed that many/most children eventually “outgrew” ADHD. With accumulating evidence that symptoms often persist into adulthood this explanation has become less attractive.
• Also, there was never any direct evidence of the perported “delay in maturation.”
• Conclusion: jury still out, but unlikely a significant factor.

Brain Dysfunction: brain is not functioning in same manner as “normal” children

• Several lines of evidence suggest abnormalities in brain functioning in populations of children diagnosed with ADHD, when compared with normal control populations:
• Neurotransmitter dysfunction or imbalances, especially selective deficiency in dopamine availability has been reported.
• Cerebral flood flow studies suggest diminished perfusion to the striatum & orbital prefrontal regions, with possibly more involvement of the right hemisphere.
• BEAM (Brain Electrical Activity Monitoring) studies have shown less electrical activation in prefrontal and frontal-limbic regions, possibly more involvement of right hemisphere.
• Neuropsychological studies has reported disinhibition of behavioral responses, suggesting possible orbital-frontal and orbital-limbic impairments.
• Conclusion: Brain dysfunction (not brain damage) appears to be a major etiological factor in ADHD.

Genetic factor explanations

• 20% to 32% of parents and siblings of children diagnosed with ADHD also show the disorder. Siblings of probands are 6 times as likely as controls to show ADHD; children of proband parent may have as high as 50% probability of diagnosis (Barkley, 1998)
• 51% to 66% concordance for ADHD in monozygotic twins; 28% to 33% concordance for dizygotic twins (Goodman & Stevenson, 1989; Sherman, Iacono, & McGue, 1997); heritability factor is estimated at approximately 0.80 (possibly up to 80% of the differences in attention, overactivity, and impulsivity between individuals with and without a diagnosis of ADHD can be accounted for genetically)
• approximately 1 in 4 diagnosed children has a biological parent diagnosed with ADHD (Zametkin, 1995)
• several studies suggest dysfunction in the dopamine system and/or underactivity of the prefrontal-striatal-limbic system; or imbalance of deopamine and serotonin; or dopomine transporter or receptor genes on several chromosomes (esp. chromosome 5, 11), (genetic heterogeneity is suggested by the high rates of comorbidity; also, ADD [as opposed to ADHD] may reflect dysfunction of posterior parietal activity, more right than left, rather than dysfunction of anterior, frontal activity [Bradshaw, 2001]). (life is not simple)
• Conclusion: Genetic (presumably hereditary) transmission appears to be a major etiological factor in ADHD.

Environmental Toxins explanations

Food Additives

• Controlled studies have suggested that a very small number of children diagnosed with ADHD (probably in range of .5 to 1%) respond very positively to diets free of color and preservative agents.

Sugar

• Controlled studies have suggested no role for refined sugar in producing ADHD symptoms (but a very large role for “expectancy effects”/placebo effects if anyone involved knows when the child is getting the real sugar).

Lead

• Usually lead poisoning leads to mental retardation and learning problems, but occasionally to ADHD like syndromes. This would fall into the Brain Damage group discussed above.

Maternal cigarette smoking during pregnancy

• Possibly a minor etiological factor, it is unclear what aspect of exposure (tars, nicotine alkaloids, reduced oxygen saturation, and/or other/unknown factors) produces the risk.
• interaction of a version of the Dopomine Transporter Gene in a male fetus and maternal smoking during pregnancy may increase risk of ADHD

Prenatal exposure to alcohol

• ADHD is associated with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE), and one of the symptoms is increased risk of ADHD. This would fall into the Brain Damage group discussed above.

Fluorescent lighting

• Controlled studies have suggested no role for exposure to fluorescent lights in producing ADHD symptoms.

Anticonvulsants

• Some seizure medications, especially Phenobarbital and Dilantin, have been reported to cause ADHD like syndromes in children. Symptoms typically remit if the anticonvulsants are discontinued. The majority of children diagnosed with ADHD have not history of seizures and have never been treated with anticonvulsant medications.

Theophylline

• Controlled studies have suggest no increased risk of ADHD symptoms in children using theophylline derivatives for treatment of asthma and other respiratory difficulties.

Conclusion: Environmental toxins appears to be a very minor etiological factor in ADHD.

Environmental & Psychosocial Factors

• Overly critical, commanding, and negative behavior has been observed in mother of children diagnosed with ADHD in informal situations and dyadic test situations. These behavioral differences, however, are not necessarily seen in the mothers’ interactions with their non-ADHD children. The suggestion is often made that these behavior differences are the result of interacting with a child showing ADHD characteristics, rather than being a cause of the difficulty.
• Some authors, however, believe that poor parenting skills and expectations for appropriate child behavior has contributed to the increased prevalence of ADHD reported by some studies.
• Conclusion: The possible role of parental and family learning influences on the initiation of ADHD symptoms is still debated. There is some consensus that families can influence these behavior, and that certain patterns of parental behavior can contribute to improvements in the children. There is much less agreement that psychosocial factors have any primary etiological role. The actions of parents can almost certainly make the child’s behavior better and worse, but probably did not “cause” it.

The big winners: neurological dysfunction involving the neurotransmitter systems and genetic transmission are the major etiological factors supported by available empirical research. These may be two facets of the same effect — what is being inherited may be problems in neurotrasport (production/release/reuptake/inhibition/metabolism) of neurotransmitters, especially those associated with frontal brain systems and the subcortical circuits associated with the frontal lobe, but this attractive hypothesis has, as yet, no direct or conclusive empirical support.

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Treatment of ADHD

(4-14-15)

Medication

• CNS Stimulant [approximate 75% effect rate, slightly higher with higher symptom thresholds for diagnosis]
  • improvement, usually not remission
  • Ritalin (methylphenidate)
    • Concerta [same drug, different delivery system]
    • Adderall
    • extended release versions
  • Dexedrine (d-amphetamine)
  • Cylert (pemoline) [use largely discontinued due to health concerns]
• non-stimulant medication for ADHD
  • Strattera (atomoxetine)
• Tricyclics (often used as antidepressants) [possibly app. 66% effect rate]; largely replaced today by SSRI’s
  • Tofranil (imipramine)
  • Norpramin (desipramine)
• Clonidine (an antihypertensive)
  • May differentially target impulsive symptoms.
• Selective Serotonin Reuptake Inhibitors (SSRI’s) (often used as antidepressant and anxiolytic agents)
  • Prozac (fluoxetine)
  • Paxil
  • Zoloft
• Anticonvulsant medications (applicability may be more in undiagnosed cases of bipolar disorder in youth)
  • Tegretal
  • gabapentin (Neurontin)
  • Dilantin
• Mood stabilizers (antimania drugs) (applicability may be more in undiagnosed cases of bipolar disorder in youth)
  • Lithium
• Atypical antipsychotic medications (neuroleptics), may be added to attempt increased control of temper/rage and/or stabilize mood
  • Risperdal
  • Geodon
  • Zyprexia

Behavioral Treatments [app. 75% effect rate]

• Home contingency management programs
• School contingency management programs
• Cognitive behavior modification for impulse control (data mixed on effectiveness)
• Social skill training (date mixed on effectiveness)

Special Education [for relief of comorbid learning disabilities]

Combinations of pharmacological and behavioral treatments

• The MTA Study
• The Multimodal Treatment Study undertaken by the NIMH was a major investigation of treatment approaches for children diagnosed with ADHD (combined type).
• This was a large scale study (almost 600 children from several cities) and yielded a large set of data, which will undoubted continue to be analyzed for several years. Initial publications appeared in 1999. A modest summary overview would include the following:
  • Reasonably managed medication intervention was an effective intervention for ADHD and had more of an impact on reducing core ADHD symptoms than a standardized, intensive behavioral intervention.
  • Medication and intensive behavioral intervention was more effective than routine psychosocial treatment.
  • The combination of medication and behavior intervention did not appear to dramatically improve on the effectiveness of medication alone (possibly, in part, because medication alone did a pretty good job: a ceiling effects) on ADHD symptoms. The combination, however, did seem more effective in improving oppositional behavior, social adjustment, parent-child relations, and reading achievement; and was associated with higher levels of family and teacher satisfaction.
• Some previous studies have yield evidence supporting a combination of pharmacological and behavioral treatment, but the added benefit from behavioral treatments have been modest at best. Part of the difficulty in drawing “simple” conclusions (e.g., “medication is better than behavior modification”, “medication and behavior mod is better than medication alone”) is that the real questions are not simple, and the answers are very dependent on the questions you ask.

Controversial treatments

• Larry Silver (2000), a psychiatrist, provides a nice discussion of “Alternative treatments for ADHD” in B.P. Guyer (Ed.), ADHD: Achieving success in school and in life. Boston: Allyn & Bacon.
• dietary: “chemical changes”
  • “Chemical changes refers to the concept of orthomolecular medicine. This is a term introduced by Linus Pauling, Referring to the treatment of mental disorders and other disorders by the provision of the optimum concentrations of substances normally present in the human body (Pauling, 1968).” (Silver, 2000)
  • Food additives: benefit for very small group (app. 1% of diagnosed cases)
  • Refined sugars–restricting sugar in diet: no merit
  • Megavitamins: no merit
  • Trace elements: no evidence and probably no merit
  • Herbs: no evidence and probably no merit
• experiential: “physiological changes”
  • “Physiological changes refers to the concept that by stimulating specific sensory inputs or exercising specific motor patterns, one can retrain, recircuit, or in some way improve the functioning of a part of the central nervous system.” (Silver, 2000)
  • Neurotherapy (EEG biofeedback treatment of ADHD): ?
    • While a number of previous published studies have reported efficacy, a number of methodological challenges have remained; Gevensleben et al. (2009) appears to address many of these. While questions still remain, neurofeedback appears to be emerging as an empirically supported treatment of ADHD
  • Patterning: no merit; demands on family may be harmful
  • Vestibular dysfunction–treatment with anti-motion-sickness medication: no merit
• other:
  • chiropractic/homeopathic/alternative medicine: I am aware of no supporting empirical literature
  • allergies: there may be a relationship between allergies and brain functioning, this is still be investigated, but–to date–treatment programs based on allergy models (other than food additive allergies) have not proved productive

Treatment of ADHD in adults

• pharmacological
• self-management

No serious investigator or clinician is satisfied with the current state of affairs regarding treatment of ADHD. The development of better treatments will undoubtedly begin as experimental and probably controversial interventions. As in all things–seperating the wheat from the chaff will be the challenge.