ADHD Overview

ADHD OverviewADHD Overview

Jeanette E. Cueva, M.D.

OverviewOverview

ADHD historyPerception and realityDiagnosis in the US and UKEtiology

ADHD in 1854: Fidgety PhilADHD in 1854: Fidgety Phil

“Let me see if he is able to sit still for once at the table.

Thus Popa bade Phil behave and Mama looked very grave

But fidgety Phil, He won’t sit still…”

http://www.fln.vcu.edu/struwwel/philipp_e.html

History of ADHDHistory of ADHD

Date Milestone

1902 Still: Description of ADHD symptoms

1937Bradley: Benzadrine. Conceptualization of ADHD involved testing response to stimulants

1955 MPH

1960 Minimal Brain Dysfunction

1980 ADD – DSM-III; adults acknowledged

1987 ADHD – DSM-III R

1994 DSM-IV

Erroneous Erroneous Beliefs/Assumptions Beliefs/Assumptions

About ADHDAbout ADHDMinor disorder if it even existsAffects almost solely malesHas little impact beyond the classroomDisappears spontaneously after grade

school

Erroneous Erroneous Beliefs/Assumptions Beliefs/Assumptions

About ADHD About ADHD Overdiagnosed

– Diagnosis made about any energetic or “different” child– Medication is only a form of chemical control

Misdiagnosed in cases of– Poor parenting– Rigid, misguided teachers

Overtreated by physicians who used powerful and potentially addicting drugs for a minor, temporary ailment

Erroneous Beliefs/Assumptions Erroneous Beliefs/Assumptions About ADHD About ADHD

Produced a pattern of treatment in which clinicians did not use medications

OR– Used low doses of medications– (Only Monday through Friday)– (Only during school hours)– (Gave “drug holidays”)– Stopped medications in adolescence

Erroneous Beliefs/Assumptions Erroneous Beliefs/Assumptions

Are FalseAre False

Erroneous Beliefs vs Erroneous Beliefs vs EvidenceEvidence

Evidence Exists to Evidence Exists to

Invalidate ThemInvalidate Them

ADHDADHD

EvidenceEvidence In the beginning, the diagnosis of ADHD was unclear due

to– Different names– Inconsistent nature of impairments– Feedback from 3rd parties (ie, children are poor historians)– Media controversy– Lack of validated diagnostic instruments

But by 1998, the AMA called ADHD “…one of the best-researched disorders in medicine, and the overall data on its validity are far more compelling than for many medical conditions.”

Goldman et al. JAMA 1998;279:1100.

Antihypertensives

Neuroleptics

Antidepressants

Stimulants

N=6472 children,

adolescents, and adults.

Controlled Studies of Controlled Studies of Medication in ADHDMedication in ADHD

Spencer et al. JAACAP 1996;35:409.

155155

21211212

33

ADHD: DiagnosisADHD: DiagnosisBased on coding systemsDSM-IV and DSM-IV TR

(www.behavenet.com/capsules/disorders/adhd.htm)

– US314.01 ADHD, Combined Type314.00 ADHD, Predominantly Inattentive Type314.01 ADHD, Predominantly Hyperactive-Impulsive Type

ICD 10 (www.mentalhealth.com/icd/p22-ch01.html)

– EU/USF90 Hyperkinetic disordersF90.0 Disturbance of activity and attentionF91.1 Hyperkinetic CD

InattentionInattention

Impulsivity/HyperactivityImpulsivity/Hyperactivity

ADHD: ADHD: Core Symptom AreasCore Symptom Areas


ADHD: DSM-IV CriteriaADHD: DSM-IV Criteria

Inattention to detail/makes careless mistakes

Difficulty sustaining attention

Seems not to listen Fails to finish tasks

Difficulty organizing Avoids tasks

requiring sustained attention

Loses things Easily distracted Forgetful

Six or more of the following – manifested Six or more of the following – manifested oftenoften

ADHD: DSM-IV CriteriaADHD: DSM-IV Criteria

Impulsivity– Blurts out answers

before question is finished

– Difficulty in awaiting turn

– Interrupts or intrudes on others

Difficulty organizing– Fidgets– Unable to stay seated– Inappropriate

running/climbing– Difficulty in engaging

in leisure activities quitely

– On the go– Talks excessively


Six or more of the following – manifested Six or more of the following – manifested oftenoften

ADHD: DSM-IV Diagnostic ADHD: DSM-IV Diagnostic CriteriaCriteria

Symptom criteria must be met for past 6 monthsSome symptoms must be present before 7 years

of ageSome impairment from symptoms must be

present in 2 or more settingsSymptoms lead to significant impairment

– Social, academic, or occupationalSymptoms are not exclusionary due to other

mental disorders

ADHD: DSM-IV SubtypesADHD: DSM-IV Subtypes

ADHD predominately inattentive type– Criteria met for inattention but not for

impulsivity/hyperactivity ADHD predominately hyperactivity/impulsivity

type– Criteria met for impulsivity/hyperactivity– but not for inattention

ADHD combined type– Criteria met for inattention and

impulsivity/hyperactivity

DSM IV Diagnosis: Clinical DSM IV Diagnosis: Clinical SubtypesSubtypes

Predominately inattentive – Easily distracted; not

excessively hyperactive or impulsive

Combined type– Predominent presentation;

exhibits all three classical signs

Predominately hyperactive-impulsive– Extremely hyperactive and

impulsive; not highly inattentive

Combined typeCombined type

Predominately Predominately hyperactive-impulsivehyperactive-impulsive

Predominately inattentivePredominately inattentive

ADHD: ICD 10ADHD: ICD 10

Stresses HK disorders over “ADD”– Implies knowledge of psychological process

and suggests anxious, preoccupied, or dreamy apathetic children

– Inattention central featureCardinal features of DSM-IV

– Vague– Diagnostic guidelines descriptive

ImpairmentImpairment

DSM-IV-TR: ADHD symptoms must be consistently and persistently impairing in at least 2 areas of life functioning– Much more than personality traits and quirks– Must significantly impair major aspects of day-

to-day life

Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. 2000.

Parent stress

Family conflict

Accidents and injuries

Smoking and substance abuse

Legal difficulties

Poor peer relationships

School failure

Psychiatric comorbidity

Impairment in ADHDImpairment in ADHD

ADHD: Variations in ADHD: Variations in symptomssymptoms

Pervasiveness

Frequency of Occurrence

Degree of impairment

DSM-IV-Defined ADHD DSM-IV-Defined ADHD Population (Paediatric 3-19 yrs)Population (Paediatric 3-19 yrs)

2000 2005 2010 2000-5 Growth (%/Yr)

2005-10 Growth (%/Yr)

United States

10,362,900 10,391,600 10,225,200 0.1 (0.3)

Europe 9,795,600 9,396,600 8,900,300 (0.8) (1.1)

France 2,185,100 2,133,200 2,082,000 (0.5) (0.5)

Germany 2,581,500 2,471,300 2,270,800 (0.9) (1.7)

Italy 1,637,200 1,565,200 1,480,300 (0.9) (1.1)

Spain 1,222,700 1,108,200 1,052,800 (1.9) (1.0)

United Kingdom

2,169,100 2,118,700 2,014,400 (0.5) (1.0)

Japan 3,432,000 3,265,600 3,233,300 (1.0) (0.2)

Major Market Total

23,590,500 23,053,800 22,358,800 (0.5) (0.6)

Source: Decision Resources, “Attention Deficit Hyperactivity Disorder”, December 2001

ADHD: World Wide Prevalence in ADHD: World Wide Prevalence in School Aged ChildrenSchool Aged Children

Prevalence (per 1000)

Diagnosis & Treatment Diagnosis & Treatment Rates of ADHDRates of ADHD

0

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

USA Europe* J apan

Prevalence

Diagnosis

Treatment

Source: Decision Resources, “Attention Deficit Hyperactivity Disorder”, December 2001 *Europe = D,F,I,UK,E

ADHD: EtiologyADHD: Etiology

ADHD is a heterogeneous behavioral disorder with multiple possible etiologies

ADHD

NeuroanatomicNeuroanatomicNeurochemicalNeurochemical

CNS CNS insultsinsults

Genetic Genetic originsorigins

Environmental Environmental factorsfactors

Twin StudiesTwin Studies

Adoption StudiesAdoption Studies

Family StudiesFamily Studies

Molecular GeneticsMolecular Genetics

Adult ADHDAdult ADHDGenetic BasisGenetic Basis

Genetic Basis of ADHD

Genetic Basis of ADHD

Heritability of ADHDHeritability of ADHDHeightSchizophrenia



ADHD





Pre- and Perinatal Risk Pre- and Perinatal Risk Factors for ADHDFactors for ADHD

Indicator of AdversityIndicator of Adversity

Low social classMaternal psychopathologyPaternal criminalityFamily conflictPlacement outside the home

Risk for Childhood Mental Risk for Childhood Mental DisturbanceDisturbance

0

1

2

3

4

5

6

7

8

9

10

1 2 4

Number of Indicators of Adversity

Od

ds

Rat

io

Rutters Indicators of Adversity Rutters Indicators of Adversity and Risk for ADHDand Risk for ADHD

0

1

2

3

4

5

1 3 4

Number of Rutter’s Indicators

Ad

just

ed O

dd

s R

atio

20

Gender, parental ADHD

Maternal smoking during pregnancy



ADHD: ADHD: Diagnostic Diagnostic ConsiderationsConsiderations

Risk Factors for ADHDRisk Factors for ADHD

GirlsBoys

ADHD: Adult Common ADHD: Adult Common Comorbid DiagnosisComorbid Diagnosis

FemaleMale

“It’s a guy thing.”

Psychiatric ComorbidityPsychiatric Comorbidity

Anxiety(34%)

Non-comorbid(55%)

CD(8 – 20%)

4%

2%

7%

MD(20 to 30%)

7%23%



ADHD





Affected area of brainAffected area of brain

MRI in Adults with ADHDMRI in Adults with ADHD

MGH-NMR Center & Harvard- MIT CITP

Bush G, et al. Biol Psychiatry. 1999;45(12):1542-1552.

ADHD: NeurochemistryADHD: Neurochemistry

ADHD best understood by the interaction of multiple neurotransmitters

Neurotransmitters most critical in ADHD

– Norepinephrine (NE)

– Dopamine (DA)

NeurotransmittersNeurotransmitters

CH2 CH2 NH2OH

OH

DopamineDopamineOH

CH CH NH2OH

OH

NorepinephrineNorepinephrine

CH2 CH NH2

CH3

AmphetamineAmphetamine

O

NH2

N

O

PemolinePemolineMethylphenidateMethylphenidate

COCH3

O

NH

http://amphetamines.com/meth.html

Storagevesicle

DA Transporter

Cytoplasmic DA

Methylphenidateinhibits

Presynaptic Neuron

Synapse

Probable Mechanism of Action of Probable Mechanism of Action of MethylphenidateMethylphenidate

Wilens and Spencer. Wilens and Spencer. Handbook of Substance Abuse: Neurobehavioral Handbook of Substance Abuse: Neurobehavioral Pharmacology.Pharmacology. 1998;501-513. 1998;501-513.

The Mechanisms of Action of The Mechanisms of Action of AmphetamineAmphetamine

Wilens and Spencer. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513.

AMPH Inhibits

AMPH is taken up into cell causing DA release into synapse

AMPH diffuses intovesicle causing DA release into cytoplasm

Presynaptic Neuron

Storagevesicle

DA TransporterProtein

Cytoplasmic DA

AMPH

AMPH

Synapse

AMPH blocks uptake into vesicle

Dopamine Neurotransmission Dopamine Neurotransmission Relative to ADHDRelative to ADHD

Enhances signalImproves attention

– Focus– On-task behavior– On-task cognition

Solanto. Stimulant Drugs and ADHD. Oxford; 2001.

Nigrostriatal Pathway

Mesolimbic Pathway

Substantia nigra

Ventral tegmental area

Mesocortical Pathway

DopamineDopamine

Locus Ceruleus

Frontal

Limbic

Norepinephrine Norepinephrine Neurotransmission Neurotransmission Relative to ADHDRelative to ADHD

• Dampens noise

• Executive operations

• Increases inhibition


NorepinephrineNorepinephrine

Catecholaminergic Neurotransmission Catecholaminergic Neurotransmission Relative to ADHDRelative to ADHD

Striatal - PrefrontalEnhances SignalImproves Attention

– Focus– Vigilance– Acquisition – On-task behavior– On-task cognitive– Perception(?)

PrefrontalDampens Noise

– Distractibility– Shifting

Executive operationsIncreases Inhibition

– Behavioral– Cognitive– Motoric

NorepinephrineNorepinephrineDopamineDopamine


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ADHD Overview