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Assessment and Diagnosis of ADHD
Joseph Biederman, MDProfessor of Psychiatry Harvard Medical School Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHDDirector, Bressler Program for Autism Spectrum DisordersMassachusetts General Hospital
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History of ADHD
1902 - George Still described ADHD Symptoms
1937 – Bradley* Benzedrine
1955 – MPH Created
1960 – Minimal Brain Dysfunction
1966 – Clements listed attention as a deficit in children
1980 – Attention Deficit Disorder + or – Hyperactivity (DSM-III)
1987 – Attention Deficit Hyperactivity Disorder (DSM-III-R)
1994 – DSM-IV updated criteria
* Bradley (1937) original conceptualization of ADHD involved testing of response stimulant.
American Psychiatric Association, 1980, 1987, 2001; Bax M, MacKeith R. London: Heinemann; 1963; Bradley C. Am J Psychiatry1937;94:577-85; Pediatrics 1950;5:24-37; Clements SD. J Lancet 1966;86:121-3. Editorial, J Atten Disord 2000;3:173-91. Still GF. Lancet 1902;1:1008-12, 1077-82, 1163-8; Stubbe DE. Child Adolesc Psychiatr Clin N Am 2000;9:469-79.
2013 – DSM-V updated criteria
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ADHD:
Etiology
ADHD is a heterogeneous behavioral disorder with multiple possible etiologies
ADHD
NeuroanatomicNeurochemical
CNS insults
Genetic origins
Environmental factors
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0 5 10 15 20Prevalence of ADHD (%)
Puerto Rico
New York City
Pittsburgh
Iowa
Tennessee
Minnesota
Oregon
Missouri
Virginia
North Carolina
N.Y., Mich., Wis.
IndiaChina
NetherlandsNew Zealand
JapanBrazil
UkraineGermany
Netherlands/BelgiumSwitzerland
IsraelUnited Kingdom
IrelandCanada
New ZealandSpain
0 5 10 15 20Prevalence of ADHD (%)
Worldwide Prevalence of ADHD in Children
Faraone SV et al. (2003), World Psychiatry 2(2):104-113
USA Ex USA
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Akinbami et al. NCHS Data Brief No. 70, August 2011
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Zuvekas al. Am J Psychiatry 2012; 169:160-166Psychopharmacology Course 2017
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• Only 13% of patients consistently take their
medication one year out
• Within 2 to 3 months, a majority of patients with ADHD have stopped taking medication consistently
• Patients renewed their monthly prescriptions about 2 to 3 times per year1
0%
20%
40%
60%
80%
100%
1 3 5 7 9 11 13 15
Month
Pa
tie
nts
(%
)
OROS MPH
MPH LA
MAS XR
Atomoxetine
Adherence in ADHD is Dismal
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Percent of Children with ADHD who Renewed their First Stimulant Rx at Partners Healthcare: An EMR Review
# of patients # of patients who refilled
a prescription for ≥1 medication
% of patients who refilled
2, 685 1, 537 57%
0
10
20
30
40
50
60
70
80
90
100
Patients who refilled a
prescription for ≥1 medication
Per
cen
t (%
)
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Poor Adherence to Treatment in ADHD
• Poor adherence occurs despite the well documented morbidity of ADHD, the marked efficacy and safety of stimulants as well as the fact that ADHD symptoms return rapidly when the medication is not taken
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Long Delays in the Initiation of Treatment (n=1498)
3.3
7.8
0
1
2
3
4
5
6
7
8
9
Age of Onset of Diagnosis Age of Onset of Treatment
p < 0.001
MGH Pediatric Psychopharmacology Clinic
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Diagnosis of ADHD
• Diagnosis is based on clinical assessment of symptoms, associated impairment and age of onset
• No test is available
• Symptoms are subjective, as well as developmentally and context sensitive
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Inattention
Impulsivity/Hyperactivity
ADHD: Core Symptom Areas
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ADHD: DSM-V Criteria
• Inattention to details/ makes careless mistakes
• Difficulty sustaining attention
• Seems not to listen
• Fails to finish tasks
Inattention
• Difficulty organizing
• Avoids tasks requiring sustained attention
• Loses things
• Easily distracted
• Forgetful
Six or more of the following manifested often:
DSM-V, 2013
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ADHD: DSM-V Criteria
Impulsivity• Blurts out answer before
question is finished
• Difficulty awaiting turn
• Interrupts or intrudes on others
Hyperactivity• Fidgets
• Unable to stay seated
• Inappropriate running/climbing (restlessness)
• Difficulty in engaging in leisure activities quietly
• “On the go”
• Talks excessively
Impulsivity/Hyperactivity
Six or more of the following manifested often:
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ADHD
Variation in Symptoms
Frequency
of Occurrence
Degree of
Impairment
Pervasiveness
Symptoms Vary in
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Course of ADHD Symptoms Over Time by Sex: A Growth Curve Model
Age by Sex Interaction: NS
Biederman et al. 2009Psychopharmacology Course 2017
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Age-Dependent Decline and Persistence of ADHD Throughout the Lifetime
Faraone et al. Nature Reviews Disease Primers 2015Psychopharmacology Course 2017
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ADHD: Course of the Disorder
Inattention
Time
Hyperactivity
Impulsivity
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ADHD as a Brain Disorder
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Faraone et al. Nature Reviews Disease Primers 2015Psychopharmacology Course 2017
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Brain Mechanisms in ADHDFaraone et al. Nature Reviews Disease Primers 2015
The executive control and cortico-cerebellar networks coordinate EFs
The DLPC is linked to WM, the VMPFC to complex decision making and strategic planning, and the parietal cortex to attention
The VMPFC, OFC & ventral striatum are the brain network associated with anticipation and reward
The frontal and parietal cortices and the thalamus support attentional functioning
Negative correlations between the DMN and the frontoparietal control network are weaker in patients with ADHD
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Hoogman at el. (ENIGMA ADHD Working Group) Lancet Psychiatry 2017 Feb 16. doi: 10.1016/S2215-0366(17)30049-4.
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ADHD Imaging Studies Summary
• Neuroimaging studies confirm that brain abnormalities in fronto-subcortical networks are associated with ADHD
• Neuroimaging techniques are not valid tools for ADHD diagnosis; imaging measures are not sensitive or specific enough to be used for diagnostic purposes
• Treatment attenuates neural deficits
Spencer et al. J Clin Psychiatry 2013 Sep;74(9):902-17
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ADHD as Neurobiological Disorder
Catecholamine Dysregulation
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Frontosubcortical Networks and Catecholamines
• Dopaminergic and noradrenergic dysregulation abnormalities in fronto subcortical pathways
• Medications that are effective in ADHD are either dopaminergic or noradrenergic
Zametkin. J Am Acad Child Adolesc Psychiatry. 1987;26(5):676-686.
Zametkin. J Am Acad Child Adolesc Psychiatry. 1987;26(5):676-686
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Human Brain From R. Barkley, Scientific American, Sept. 1998, p. 47
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MESENCEPHALON
PONS
MEDULLARaphe nuclei(serotonin)
Substantia nigra tegmentum(dopamine)
Locus ceruleus(norepinephrine)
to cerebellum
to cord
to diencephalon and cerebrum
Brain Stem
Psychopharmacology Course 2017
www.mghcme.orgPsychopharmacology Course 2017
www.mghcme.orgBusiness Week, 1999
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GeneticBasisof ADHD
ADHD: Genetics
Twin Studies Family Studies
Adoption Studies Molecular Genetics
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Family Studies
0 5 10 15 20 25 30
Morrison &Stewart (1971)
Cantwell (1972)
Biederman et al
(1990)
ADHD group Control group
ADHD in first-degree family members of children with ADHD
Percent
0 0.2 0.4 0.6 0.8 1
Matheny 1971
Willerman 1973
Goodman 1989
Gillis 1992
Edelbrock 1992
Stevenson 1992
Schmitz 1995
Thapar 1995
Gjone 1996
Silberg 1996
Sherman 1997
Levy 1997
Nadder 1998
Hudziak 2000
Willcutt 2000
Thapar 2000
Coolidge 2000
Kuntsi 2001
Martin 2002
Rietveld 2003
Laarson 2004
Cole 2009
Bornovalova 2010
Illott 2010
Heritability
Schizophrenia HeightPanic Disorder
Mean Heritability of ADHD in Youth=.75
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Genetics of ADHD
Faraone et al. Nature Reviews Disease Primers 2015Psychopharmacology Course 2017
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Dopamine Transporter
(DAT)
Dopamine
Receptor
(DRD4)
Presynaptic Neuron
Methylphenidate
(MPH)
Dopamine
The Dopamine Story...
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New Results from GenomewideAssociation Studies (GWAS)
0
10
,00
020
,00
030
,00
040
,00
0
Y2012 Y2014 Q4_2015 Q1_2019
Number of ADHD GWAS Samples
Faraone et al, 2015Psychopharmacology Course 2017
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Preliminary ADHD meta-analysis18,284 cases 33,836 controls
Preliminary analyses suggest eight genome-wide significant lociPGC ADHD/iPSYCH-SSI-Broad CollaborationPsychopharmacology Course 2017
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Maternal Smoking During Pregnancy:Results in Children
0
5
10
15
20
25
His
tory
of
Mat
ern
al
Smo
kin
g (%
)
* P=0.04, controlling for SES, parental ADHD, and parental IQ
P=0.00222%
ADHD ( N=140)
8%
Controls ( N=120)
Milberger et al. Am J Psychiatry 1996;153:1138.
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ADHD Diagnostic Considerations
Inattention
Impulsivity/Hyperactivity
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0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Cu
mu
lati
ve M
orb
idit
y R
isk
Control ADHD
P ≤ .009 for all categories
Biederman et al. Psychological Medicine, 2006, 36, 167–179.
Cumulative Morbidity Risks for Psychiatric Disorders in ADHD and Control Probands
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Biederman et al. AJP. April 2010Psychopharmacology Course 2017
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Accidents and Near Misses
0%
10%
20%
30%
40%
50%
60%
70%
80%
Accident Accident and Near Misses
Pro
bab
ilit
y o
f A
ccid
en
t
P<0.05*
P<0.05*
*Indicates P<0.05 after controlling for gender, age, time of day and the age*ADHD interaction
(Reimer et al., submitted)
ADHD ADHD
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Percent of Subjects Involved in Collisions During Surprise Events
LDX = lisdexamfetamine dimesylate
Biederman et al. 2011 submitted
*
During the five surprise events, drivers in the medication group were 67% less likely to have a collision than drivers in the placebo group
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Chang et al. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.0659
Published online May 10, 2017.
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ADHD:
Impact on Family
Parents of children with ADHD experience higher levels of
Mash and Johnston. J Clin Child Psychol 1990;19:313.Murphy and Barkley. Am J Orthopsychiatry 1996;66:93.
• Stress
• Self-blame
• Social isolation
• Depression
• Marital discord
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Status of 144 Caregivers at any time after Diagnosis of Child’s ADHD
Noe et al. 1999
Changed Work Status
39%
63%
Unchanged Work Status
Parent stress
Family conflict
Accidents and injuries
Smoking and substance abuse
Legal difficulties
Poor peer relationships
School failure
Psychiatric comorbidity
Impairment in ADHD
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Is ADHD a Serious Public Health Concern?
Public Health Significance
Prevalence
Treatment Effectiveness
Chronicity
Impairment
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Summary
• ADHD is a neurobehavioral disorder with a:– Complex etiology– Neurobiologic basis– Strong genetic component
• ADHD – Affects millions of people of both genders– Persists through adolescence and adulthood in a high
percentage of cases– Can have negative impact on multiple areas of
functioning– ADHD is a highly treatable disorder
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QUESTIONS ?