is there a late onset form of adhd? · defining adult adhd (dsm-5) criteria a: 5 or more symptoms...
TRANSCRIPT
Philip Asherson MRCPsych, PhD
Professor of Molecular Psychiatry & Honorary
Consultant Psychiatrist,
MRC Social Genetic Developmental Psychiatry,
Institute of Psychiatry, UK
MRC Social Genetic and
Developmental Psychiatry
Is there a late onset form of ADHD?
Diagnostic criteria
What is ADHD
A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development
What is not ADHD
The symptoms are not solely a manifestation of oppositional behaviour, defiance, hostility, or failure to understand tasks of instructions
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, 2013
Criteria for Adult ADHD Diagnosis: DSM-5
Inattention Lack of attention to details, makes careless
mistakes
Difficulty sustaining attention
Does not listen when spoken to directly
Trouble completing or finishing job tasks
Problems organizing tasks and activities
Avoids or dislikes sustained mental effort
Loses and misplaces things
Easily distracted
Forgetful in daily activities
Hyperactivity Fidgetiness b(hands or feet) or squirming in
seat
Leaves seat when not supposed to
Restless or overactive
Difficulty engaging in leisure activities quietly
Always ‘on the go’
Talks excessively
Impulsivity
Blurts out answers before questions have been completed
Difficulty waiting in line or taking turns
Interrupts or intrudes on others when they are working or busy
American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition
2013
DSM-5: Age-appropriate descriptions of ADHD
Inattention
• Mind elsewhere in the absence of obvious distractions
• Starts tasks, quickly loses focus, easily side-tracked
• Fails to finish tasks in the workplace
• Reporting task unrelated thoughts (mind wandering)
• Problems returning calls, paying bills
• Poor time management, not meeting deadlines
Hyperactivity
• Feeling restless
• Feeling uncomfortable being sat in restaurants or meetings
Impulsivity
• Butting into conversations or activities
• Intrude into and take over what other people are doing
American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013
Defining Adult ADHD (DSM-5)
● Criteria A: 5 or more symptoms of inattention or hyperactivity-impulsivity
● Criteria B: Several symptoms present by the age of 12
● Criteria C: Several symptoms present in two or more settings
● Criteria D: Symptoms interfere with or reduce quality of social, educational or occupational functioning
● Criteria E: Symptoms are not better explained by another condition, such as mood disorder
American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013
6 6
1. *Work Functions 2. *Social relationships 3. *Coping with daily activities 4. Driving accidents (increased mortality) 5. *Behavioural problems 6. *Distress from the symptoms 7. *Low self-esteem 8. Emotional instability 9. Sleep problems 10. *Risk for comorbid disorders (substance abuse, anxiety, depression,
personality disorder) 11. Cognitive impairments, including general and specific learning
difficulties (dyslexia, dyspraxia, autism spectrum disorder)
Domains of ‘IMPAIRMENT’
NICE Clinical Guideline 72. 2008. http://guidance.nice.org.uk/cg72;
Asherson P, Expert Rev Neurotherapeutics. 2005 Jul;5(4):525-39.
Psychosocial
Psychiatric
Neurodevelopmental
(* NICE definition of impairment 2008)
Population prevalence rates
Polanczyk et al 2007
5.29%
Prevalence of ADHD in children
8.8
6.1
13.3
7.1
12.9
5.7 5.9
0
2
4
6
8
10
12
14
DSM_IV subtype Prevalence Male : Female
Combined 3.4 2.7 : 1
Inattentive 1.8 1.8 : 1
Hyper-imp 0.8 3.5 : 1
Willcutt Neurotherapeutics (2012) 9: 490-499
percent
Assuming 5% prevalence of ADHD during middle childhood and 50% decline every 5 years • Estimated prevalence age 20 = 0.84% • Estimated prevalence age 30 = 0.21% • Estimated prevalence age 50 = 0.01%
Hill and Schoener
Developmental delay
5 10 15
NORMAL
ADHD
AGE
ADHD symptoms
Developmental deficit
5 10 15
NORMAL
ADHD
AGE
ADHD symptoms
Does ADHD persist?
ADHD symptom scores at 7 and 17 years
0 0.2 0.4 0.6 0.8 1 1.2
Control
ADHD
Age 17 years
Age 7 years
Taylor et al. 1996 Scores from PACAS interview
The age-dependent decline and persistence of attention-
deficit/ hyperactivity disorder throughout the lifetime
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder
Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
Estimates of adult ADHD prevalence based on longitudinal follow-up studies
Faraone meta-analysis 2006 • Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%
• In partial remission: 5% x 0.65 = 3.3%
Prevalence of ADHD from US National Comorbidity Survey
Estimated prevalence of 4.4%
Kessler et al 2006, AmJPsych
• Six symptoms of either inattention or hyperactivity-impulsivity during last 6 months (A)
• Two or more symptoms before age 7 (B) • Some impairment in at least two areas of living during
the past 6 months (C) • Clinically significant impairment in at least one of these
areas (D).
Prevalence of adult ADHD
Fayyad et al., Br J Psychiatry. 2007 May;190:402-9.
4.1%
1.9%
7.3%
3.1%
2.8%
1.8%
1.9%
5%
1.2%
5.2%
3.4%
0 1 2 3 4 5 6 7 8
Belgium
Colombia
France
Germany
Italy
Lebanon
Mexico
Netherlands
Spain
USA
TOTAL
• Prevalence = 2.5% (95% CI: 2.1–3.1%)
Simon et al. Br J Psychiatry. 2009 Mar;194(3):204-11
Prevalence of adult ADHD
Estimates of adult ADHD prevalence based on longitudinal follow-up studies
Faraone meta-analysis 2006 • Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%
• In partial remission: 5% x 0.65 = 3.3%
Potential problems with studies so far
• Child ADHD studies: clinical samples influenced by referral bias
• Adult ADHD studies: depend on retrospective recall
Dunedin Longitudinal Outcome Study
Child ADHD: follow-forward Adult ADHD: follow-back
Dunedin Child ADHD diagnosis n=61 (6% of sample)
• DSM-III diagnoses established in 1984 – 1988
• Assessments by child psychiatrists (age 11-13) and researchers (age 15) using DISC
• Parent/teacher ratings at ages 11, 13 and 15
• 8 or more symptoms rated by two sources (2/3 of cases) or one source (1/3 of cases)
• Onset before the age of 7 years
Dunedin Adult’ ADHD diagnosis n=31 (3% of the sample)
• Assessments in 2010-2012 aged 38
• Structured diagnostic interview with clinically trained research staff
• Based on behaviour/symptoms in last 12 months
• Blind to prior data
• DSM-5 criteria applied
• Included age adjustments (e.g. difficulty sitting through meetings, feeling restless)
• Informant ratings for childhood and adulthood
6% of the total sample met child ADHD diagnosis
5% met adult ADHD criteria
6% of the total sample met child ADHD diagnosis
5% met adult ADHD criteria
3% of the total sample met adult ADHD diagnosis
10% met child ADHD criteria
Child onset ADHD vs Adult onset ADHD
Child ADHD (n=61, 6%)
Adult ADHD (n=31, 3%)
% male 87.7% (p<.001) 61.3% (ns)
Cognitive impairments in childhood
YES (p<.001) NO (ns)
Cognitive impairments in adulthood
YES (p<.001) NO (ns)
Associated with ADHD genetic risk score
YES (p=.04) NO (ns)
Life impairment at the age of 38 Yes (p<.001) Yes (p<.001)
Questions
(1) Do children with ADHD grow out of the disorder by the age of 38 years?
(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?
Questions
(1) Do children with ADHD grow out of the disorder by the age of 38 years?
(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?
Child ADHD group
Adult ADHD group
INATTENTION
Number of ADHD symptoms reported by adults at age 38 years
Moffitt et al., 2015 Am J Psychiatry
Child ADHD group
Adult ADHD group
INATTENTION HYPER-IMPULSIVITY
Number of ADHD symptoms reported by adults at age 38 years
Moffitt et al., 2015 Am J Psychiatry
-0.2
0
0.2
0.4
0.6
0.8
1
Inattention
Hyperactivity-impulsivity
Controls Child ADHD Adult ADHD
Parent report for ADHD symptoms at the age of 38
Both p<.001
Moffitt et al., 2015 Am J Psychiatry
Do children with ADHD grow out of the disorder by adulthood?
NO
• Still cognitively impaired
• Still functionally impaired
• Still have high levels of ADHD symptoms according to parents
The only inconsistent finding are ADHD symptoms according to self-report
Moffitt et al., 2015 Am J Psychiatry
79
0
10
20
30
40
50
60
70
80
90
DSM-IV ADHD Combinedsubtype
Inattentivesubtype
Hyper-impsubtype
ResidualADHD
• Mean age at baseline assessment = 11.8 (SD=2.9; range = 6-17) • Mean age at follow-up assessment = 18.5 (SD=2.0; range = 12-26)
Percentage persistence of children/adolescents with DSM-IV ADHD: Follow-up period ~6.5 years
Cheung, Rijdijk, McLoughlin, Asherson, Kuntsi (2015) BJPsych, 2015
%
Du Rietz et al. 2016, J Psych Res
ADHD Persistent
(N)
ADHD Remittent
(N)
ADHD Persistence rate
Parent report
87 23 79%
Self report 48 60 44%
Self report leads to lower ADHD persistence rate than parent report
IQ
DSF
DSB
RTV
OE
CE
CNV
Cue-P3
Nogo-P3
Delta
Theta
Alpha
Beta
Movement intensity
Movement count
Parent Self
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Cheung et al. (2015) British Journal of Psychiatry; Du Rietz et al. 2016, J Psych Res
Remittent vs Control Remitted vs Persistent
Remitted vs Persistent Remittent vs Control
IQ
DSF
DSB
RTV
OE
CE
CNV
Cue-P3
Nogo-P3
Delta
Theta
Alpha
Beta
Movement intensity
Movement count
Parent Self
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Cheung et al. (2015) British Journal of Psychiatry; Du Rietz et al. under review
Number of Neural and Cognitive markers showing significant group vs control differences
Parent rated ADHD status
Self rated ADHD status
Persistent vs remitted
8 1
Remitted vs controls
0 10
Dynamic switching between task positive and negative networks
Uddin L.Q. 2014, Nature Reviews Neuroscience
Default mode network Salience network Executive control
Faraone et al. 2000; Chen et al., NPG, 2008
Family studies
Risk to parents Risk to siblings
14.7
2.8
20
4.7
12.7
1.4
0
5
10
15
20
25
ADHD Control ADHD Control ADHD-CT Control
RR: 5.25 4.3 9.1
ADHD symptoms scores are
highly heritable
0 0.2 0.4 0.6 0.8 1
Willerman 1973
Matheny 1980
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
Boomsma 2003
Heritability
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Co
rrela
tio
ns (r)
MZ twins DZ twins
Monozygotic/Dizygotic twins:
Correlations for Teacher ADHD rating scales
Identical twins (monozygotic): correlation ~ 76%
Non-identical twins (dizygotic): correlation ~ 35%
Asherson, unpublished data
DZ twins MZ twins
New ADHD meta-analysis 18,284 cases 33,836 controls
10 loci 8 look robust On the path!
Adult twin studies
1. Van Den Berg et al. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(1):55-60; 2. Boomsma et al. 2010; PLoS ONE 5(5): e10621. 3. Larsson et al, JAMA Psychiatry 2011
Phenotype Self-ratings Age Heritability
ADHD (study 1) Self 18-30 0.40
ADHD (study 2) Self 18+ 0.30
ADHD (study 3) Self 20-28 0.39
ADHD (study 3) Self 29-37 0.35
ADHD (study 3) Self 38-46 0.33
Heritability rates based on concordance rates for ADHD diagnosis on Swedish national medical records
Larsson et al., 2013, Psychological Medicine
0.88
0.72
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Heritability overall Heritability in adults
Heritability
Questions
(1) Do children with ADHD grow out of the disorder by the age of 38 years?
(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?
Two other population studies UK study Brazil study
Age at ADHD 5 - 12 18 11 18-19
Number in sample 2232 4426
Prevalence of child ADHD 11% 8.9%
Prevalence of adult ADHD 7.4% 12.2%
% child ADHD with adult ADHD 21.9% 17.2%
% adult ADHD with child ADHD 67.5% 12.6%
ASSESSMENTS
Child assessment Parent or teacher reported ADHD
Parent rated SDQ
Adult assessment Participant interview Participant interview
Agnew-Blais, JAMA Psychiatry, 2016; Caye, JAMA Psychiatry, 2016
Is there an adult onset form of ADHD?
POSSIBLY but…..
- Rater effects: self-versus informant
- False positive paradox
- Neurodevelopmental origins - 1/3 had oppositional defiant, conduct disorder or school failure
- Subthreshold cases in childhood, with ADHD emerging later in life
Late onset and full ADHD had similar patterns of: - Impairment - Psychiatric comorbidities - Functional impairment - Familial risks
0%
10%
20%
30%
40%
50%
60%
70%
7-9 years 7-12 years > 12 years
Faraone et al., 2006, Am J Psych
SAIL Father SAIL Mother
Bimodal distribution for self-reported age of onset of
adult ADHD symptoms in a population sample
Howe-Forbes, PhD, KCL, 2004
Possible causes of late onset ADHD
• Scaffolding during childhood/adolescence - greater demands on ‘executive functioning’
• High IQ masking impairments
• Maturational delay/failure during adolescence (e.g. executive control)
• Head injury
• Sleep disorders
• Toxins or drugs
Default Mode Network
My mind is: Constantly daydreaming
In a fog A whirlwind of thoughts
Hamster on a wheel Jack in the box
Waves in a storm Flitting and jumping
Asherson, Expert Review, 2005
Words used to describe mind wandering by adults with ADHD
Mind Wandering in ADHD
“People with ADHD often struggle with filtering out”
Traffic noise Conversations Laughter
Is it my fault Can I do my job Do you still love me
Creativity Versatility Humour
Components of Excessive Mind Wandering in ADHD
• Thoughts on the go all the time
• Thoughts jumping of flitting from one topic to another
• Multiple lines of thoughts at the same time
Context regulation Sensitive to
reward
The decoupled brain: The brain does not detect sensory visual and other stimuli during periods of mind wandering
Baird et al., 2014, J Cog Neurosci.
Performing
tasks
Performing
tasks
Inattentive
behaviour
Performing
tasks
Sleep
problems
Inattentive
behaviour
Performing
tasks
Sleep
problems
Inattentive
behaviour
Self-
awareness
and control
of behaviour
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Creativity, Occupation, Mind wandering, and Education (COME-on!!)
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