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ADHD Overview
Jeanette E. Cueva, M.D.
Overview

ADHD history
 Perception and reality
 Diagnosis in the US and UK
 Etiology
ADHD 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 ADHD
Date
Milestone
1902
Still: Description of ADHD symptoms
1937
Bradley: 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
Beliefs/Assumptions
About ADHD

Minor disorder if it even exists
 Affects almost solely males
 Has little impact beyond the classroom
 Disappears spontaneously after grade
school
Erroneous
Beliefs/Assumptions
About ADHD
 Overdiagnosed
– Diagnosis made about any energetic or “different” child
– Medication is only a form of chemical control
 Misdiagnosed in cases
– Poor parenting
– Rigid, misguided teachers
 Overtreated
of
by physicians who used powerful and
potentially addicting drugs for a minor, temporary
ailment
Erroneous Beliefs/Assumptions
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 vs
Evidence
Erroneous Beliefs/Assumptions
Are False
ADHD
Evidence Exists to
Invalidate Them
Evidence

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.
Controlled Studies of
Medication in ADHD
Stimulants
21
155
Antidepressants
12
3
Neuroleptics
Antihypertensives
N=6472 children,
adolescents, and adults.
Spencer et al. JAACAP 1996;35:409.
ADHD: Diagnosis
 Based
on coding systems
 DSM-IV and DSM-IV TR
(www.behavenet.com/capsules/disorders/adhd.htm)
– US
314.01 ADHD, Combined Type
 314.00 ADHD, Predominantly Inattentive Type
 314.01 ADHD, Predominantly Hyperactive-Impulsive Type

 ICD 10 (www.mentalhealth.com/icd/p22-ch01.html)
– EU/US
F90 Hyperkinetic disorders
 F90.0 Disturbance of activity and attention
 F91.1 Hyperkinetic CD

ADHD: Core Symptom Areas
Inattention
Impulsivity/Hyperactivity
ADHD: DSM-IV Criteria
Inattention
Six or more of the following – manifested often

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
ADHD: DSM-IV Criteria
Impulsivity/Hyperactivity
Six or more of the following – manifested often

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
ADHD: DSM-IV Diagnostic
Criteria
 Symptom
criteria must be met for past 6 months
 Some symptoms must be present before 7 years
of age
 Some impairment from symptoms must be
present in 2 or more settings
 Symptoms lead to significant impairment
– Social, academic, or occupational
 Symptoms
are not exclusionary due to other
mental disorders
ADHD: 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
Subtypes

Predominately inattentive
– Easily distracted; not
Predominately inattentive
excessively hyperactive or
impulsive

Combined type
– Predominent presentation;
exhibits all three classical
signs

Predominately hyperactiveimpulsive
– Extremely hyperactive and
impulsive; not highly
inattentive
Combined type
Predominately
hyperactive-impulsive
ADHD: ICD 10

Stresses HK disorders over “ADD”
– Implies knowledge of psychological process
and suggests anxious, preoccupied, or dreamy
apathetic children
– Inattention central feature

Cardinal features of DSM-IV
– Vague
– Diagnostic guidelines descriptive
Impairment

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.
Impairment in ADHD
Psychiatric comorbidity
School failure
Poor peer relationships
Legal difficulties
Smoking and substance abuse
Accidents and injuries
Family conflict
Parent stress
ADHD: Variations in
symptoms
Pervasiveness
Frequency of Occurrence
Degree of impairment
DSM-IV-Defined ADHD
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
School Aged Children
Netherlands, 2000
Brazil, 1999
USA, 1996
Spain, 1995
Switzerland, 1998
UK, 1991
Ontario, 1989
NZ 1987
Puerto Rico, 1998
Ireland 1991
Gemany, 1990
0
2
4
6
Prevalence (per 1000)
8
10
Diagnosis & Treatment
Rates of ADHD
12,000,000
10,000,000
8,000,000
Prevalence
6,000,000
Diagnosis
4,000,000
Treatment
2,000,000
0
USA
Europe*
Source: Decision Resources, “Attention Deficit Hyperactivity Disorder”, December 2001
Japan
*Europe = D,F,I,UK,E
ADHD: Etiology
ADHD is a heterogeneous behavioral disorder
with multiple possible etiologies
Genetic
origins
Neuroanatomic
Neurochemical
ADHD
CNS
insults
Environmental
factors
Adult ADHD
Genetic Basis
Twin Studies
Family Studies
Genetic Basis of
ADHD
Adoption Studies
Molecular Genetics
Heritability of ADHD
Schizophrenia Height
Hudziak 2000
Nadder 1998
Levy 1997
Sherman 1997
Silberg 1996
Gjone 1996
Thapar 1995
Schmitz 1995
Edelbrock 1992
Gillis 1992
Goodman 1989
Willerman 1973
0
0.2
0.4
0.6
Heritability
0.8
1
ADHD: Etiology
ADHD is a heterogeneous behavioral disorder
with multiple possible etiologies
Genetic
origins
Neuroanatomic
Neurochemical
ADHD
CNS
insults
Environmental
factors
Pre- and Perinatal Risk
Factors for ADHD
Parental CD
Parental ADHD
Parental IQ
Age at birth
SES
Psychosocial adversity
Low birth weight
Drug exposure
Alcohol exposure
Cigarette exposure
0
2
4
6
8
Odds Ratio (ADHD versus Control)
10
Indicator of Adversity

Low social class
 Maternal psychopathology
 Paternal criminality
 Family conflict
 Placement outside the home
Risk for Childhood Mental
Disturbance
10
9
8
7
6
5
4
3
2
1
0
1
2
4
Number of Indicators of Adversity
Rutters Indicators of Adversity
and Risk for ADHD
5
Gender, parental ADHD
4
Maternal smoking during pregnancy
3
2
1
0
0
1
2
3
4
Number of Rutter’s Indicators
ADHD: Diagnostic
Considerations
Inattention
Impulsivity/Hyperactivity
Risk Factors for ADHD
Boys
Girls
Learning
disorder
Anxiety
disorder
Mood disorder
CD
ODD
0
20
40
60
Prevalence Rate in Children with ADHD (%)
ADHD: Adult Common
Comorbid Diagnosis
Male
Female
Alcohol/drug
dependency
Anxiety
disorder
Mood disorder
AntiSocial
disorder
0
20
40
60
Life-time Prevalence Rates in Adults with ADHD (%)
“It’s a guy thing.”
Psychiatric Comorbidity
Anxiety
(34%)
MD
(20 to 30%)
7%
23%
7%
4%
CD
(8 – 20%)
Non-comorbid
(55%)
2%
ADHD: Etiology
ADHD is a heterogeneous behavioral disorder
with multiple possible etiologies
Genetic
origins
Neuroanatomic
Neurochemical
ADHD
CNS
insults
Environmental
factors
Affected area of brain
MRI in Adults with ADHD
MGH-NMR Center & Harvard- MIT CITP
Bush G, et al. Biol Psychiatry. 1999;45(12):1542-1552.
ADHD: Neurochemistry
 ADHD
best understood by the interaction of
multiple neurotransmitters
 Neurotransmitters most critical in ADHD
– Norepinephrine (NE)
– Dopamine (DA)
Neurotransmitters
Dopamine
Norepinephrine
OH
OH
CH2
CH2
NH2
OH
OH
CH
NH2
OH
Amphetamine
CH2
CH
CH
CH3
NH2
Methylphenidate
Pemoline
O
O
COCH3
N
O
NH
NH2
Probable Mechanism of Action of
Methylphenidate
Wilens and Spencer. Handbook of Substance Abuse: Neurobehavioral
Pharmacology. 1998;501-513.
Presynaptic Neuron
Storage
vesicle
Cytoplasmic DA
DA Transporter
Synapse
Methylphenidate
inhibits
The Mechanisms of Action of
Amphetamine
Wilens and Spencer. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513.
Presynaptic Neuron
AMPH blocks
uptake into vesicle
AMPH diffuses into
vesicle causing DA
release into cytoplasm
AMPH
AMPH
Storage
vesicle
Cytoplasmic DA
AMPH is taken up
into cell causing DA
release into synapse
DA Transporter
Protein
Synapse
AMPH Inhibits
Dopamine Neurotransmission
Relative to ADHD
Dopamine
Nigrostriatal Pathway

Enhances signal
 Improves attention
– Focus
– On-task behavior
– On-task cognition
Mesolimbic Pathway
Substantia nigra
Mesocortical
Pathway
Ventral
tegmental
area
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
Norepinephrine
Neurotransmission
Relative to ADHD
Norepinephrine
• Dampens noise
• Executive operations
• Increases inhibition
Frontal
Limbic
Locus Ceruleus
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
Catecholaminergic Neurotransmission
Relative to ADHD
Dopamine
Striatal
- Prefrontal
Enhances Signal
Improves Attention
–
–
–
–
–
–
Focus
Vigilance
Acquisition
On-task behavior
On-task cognitive
Perception(?)
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
Norepinephrine
Prefrontal
Dampens Noise
– Distractibility
– Shifting
Executive
operations
Increases Inhibition
– Behavioral
– Cognitive
– Motoric
Questions