working with difficult children: recent advances in adhd eric taylor king’s college london...
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Working with difficult children: Recent advances in ADHD
Working with difficult children: Recent advances in ADHD
Eric TaylorEric Taylor
King’s College London Institute of PsychiatryKing’s College London Institute of Psychiatry
There are many ways in which children can be ‘difficult’: ADHD is just one. Behaviour is dysregulated : inattention, executive
dysfunction, altered response to reward, poor time perception, and response disorganisation can all be involved. Assessment can guide
education, help counselling, and lead to treating ADHD.
Lessons from researchLessons from research
It’s not their faultIt’s not their fault Psychological treatments workPsychological treatments work Medicines help the worst affectedMedicines help the worst affected Increasing range of medicinesIncreasing range of medicines
More ‘diagnoses’ for child troubles
BBC to apologise for child drug program
Born mad or made bad? Crime and
the child
Conflicts in understanding ADHD*Conflicts in understanding ADHD* Genetic influences 80%;Genetic influences 80%; Frontal, striatal, Frontal, striatal,
cerebellar parts of brain cerebellar parts of brain are smallare small
Same structures Same structures underactivateunderactivate
Psychological deficitsPsychological deficits
Great differences over Great differences over timetime
Great differences in Great differences in prevalence between prevalence between countriescountries
Emotional & Emotional & behavioural problemsbehavioural problems
Performance variablePerformance variable
Persistent and pervasive abnormalities in : Attention (distractible, forgetful, disorganised); Activity (restless, fidgety) and Impulsiveness
(acting without thinking)
Where does ADHD come from?Twin studies show high heritabilityWhere does ADHD come from?Twin studies show high heritability
Twin
correlations
DZ MZ
Median heritability (13 studies) 0.82 (0.52-0.98)
Search for high-risk allelesSearch for high-risk alleles DRD4DRD4
metaanalysis p< .00000001metaanalysis p< .00000001 Odds ratio (averaged): 1.32Odds ratio (averaged): 1.32
DAT1DAT1 metaanalysis p<.0001metaanalysis p<.0001 Odds ratio (averaged): 1.13Odds ratio (averaged): 1.13
8 candidate genes well established to be associated with ADHD:
mostly affecting dopamine or serotonin neurotransmission
7 (vs 2-5 or 8) copies of 48 bp VNTR on 11p.15.5
9 vs 10 copies of 40 bp VNTR on 5p15.3
Genome scan identifies a spot on Chr 16: Cadherin 13Genome scan identifies a spot on Chr 16: Cadherin 13
Cadherins mediate cell adhesion and play a fundamental role Cadherins mediate cell adhesion and play a fundamental role in normal development. They participate in the maintenance in normal development. They participate in the maintenance of proper cell-cell contactsof proper cell-cell contacts
CDH13 also implicated in substance misuse:CDH13 also implicated in substance misuse:
Nicotine dependenceNicotine dependence
Substance dependenceSubstance dependence
Plays a role in cell adhesion, cell-cell contacts and cell-Plays a role in cell adhesion, cell-cell contacts and cell-migrationmigration
What is inherited?What is inherited?
NotNot ADHD: ADHD: genetic influences on continuum*genetic influences on continuum* NotNot a unitary trait: influences vary with context a unitary trait: influences vary with context Dispositions to react:Dispositions to react:
gene-environment interactions and correlationsgene-environment interactions and correlations early physical environmental associationsearly physical environmental associations parenting influences on developmentparenting influences on development MAOA multiplies effects of violence, DRD4.7/DAT10 of MAOA multiplies effects of violence, DRD4.7/DAT10 of
smokingsmoking
*(with possible exception at highest level of severity & possible latent classes)
Probable environmental associationsProbable environmental associations
PregnancyPregnancy nicotine, alcohol, anticonvulsants, cocainenicotine, alcohol, anticonvulsants, cocaine lead, mercury; thyroid, immune rejectionlead, mercury; thyroid, immune rejection stress; infections; toxaemia;APHstress; infections; toxaemia;APH
PerinatalPerinatal low birth weight, O.C.s, perinatal care, [season of birth]low birth weight, O.C.s, perinatal care, [season of birth]
Infancy Infancy attachment problems, neglect, injuryattachment problems, neglect, injury socioeconomic adversity, nutritionsocioeconomic adversity, nutrition
ChildhoodChildhood Course influenced by exclusion, hostility, injury, schoolCourse influenced by exclusion, hostility, injury, school
Embryonic Postnatal
Week: 0 6 12 18 24 30 36 Month: 0 6 12 18 24 30 36 Year: 4 8 12 16 20 24
Cell Birth
Migration
Axonal/Dendritic Outgrowth
Programmed Cell Death
Myelination
Majority of Neurons
Fewer Neurons, primarily in cortex
Synaptic Production
Synaptic Elimination/Pruning
10 cm
But, if ADHD is so neurological, how come it varies so much in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?
Prevalence of disorderPrevalence of disorder
Administrative prevalence from local surveys; HKD in approx 105,000 nationally
0
10
20
30
40
50
Nu
mb
ers
pe
r 1
00
0
US'80 UK'80 US'98 UK'99
Admin prevalence Hyperkinetic disorder
ADHD /1000
Real prevalence
Prevalence of disorderPrevalence of disorder
Same survey method in Hong Kong and East London
0
10
20
30
40
50
60
70
Nu
mb
ers
pe
r 1
00
0
HKratings
UKdiag
HK ratings UK ratings HK diag UK diag
Is it a Social Problem?Is it a Social Problem?Is it a Social Problem?Is it a Social Problem?
Does society determine the presence of ADHD?Does society determine the presence of ADHD? No, shared environment plays little partNo, shared environment plays little part
Does society alter the rate?Does society alter the rate? Only small differences between societiesOnly small differences between societies Little increase over timeLittle increase over time
Does society determine what is recognised?Does society determine what is recognised? Yes, substantial cultural differencesYes, substantial cultural differences
Interventions in the classroomInterventions in the classroom
Proximity to teacherProximity to teacher Managed transitionsManaged transitions Pacing & letting off energyPacing & letting off energy Classroom aideClassroom aide
operant conditioningoperant conditioning peer advicepeer advice
Rule governmentRule government Clarity of goal & speed of feedbackClarity of goal & speed of feedback Understanding disorder (eg projects)Understanding disorder (eg projects) Monitoring medicationMonitoring medication
Some common-sense procedures – avoiding distractors and short-chunk learning – don’t yet have trial evidence
Specific treatmentsSpecific treatments
Psychological therapies:Psychological therapies: Parent training, behaviour mod, social skillsParent training, behaviour mod, social skills
Licensed drugs:Licensed drugs:Methylphenidate, dexamfetamine, Methylphenidate, dexamfetamine,
atomoxetineatomoxetine Unlicensed drugs:Unlicensed drugs:
Trial evidence:Trial evidence: pemoline, imipramine, clonidine, bupropion, pemoline, imipramine, clonidine, bupropion, “Adderall”, modafinil, guanfacine“Adderall”, modafinil, guanfacine
Anecdotal: Anecdotal: moclobemide, risperidone, sertraline moclobemide, risperidone, sertraline
Diet: Diet: eliminations and supplementseliminations and supplements
Include non-specific interventions - education, support, advice
Xavier, aged 11, has been out of the control of his parents after an episode of meningoencephalitis at age 4. He is dangerously aggressive to his sister and younger brother and has been excluded from a special unit at school. He sets fires, steals from shops, and puffs cannabis with a group of older boys.He can’t concentrate in class, is very forgetful and disorganised; and teachers have believed that this comes from a chaotic home background.
A range of presentations: XavierA range of presentations: Xavier
A complex disorder, multiply causedA complex disorder, multiply caused
Not just genetic: The Environmental Risk Longitudinal Twin Study interviewed the mothers of 565 five-year-old monozygotic (MZ) twin pairs : the twin receiving more maternal negativity and less warmth had more antisocial behavior problems. (Moffitt et al 2008)
Not just bad parents: Medication of child reduces parental EE
Not just complications:Not just complications:In never-medicated adults:In never-medicated adults:Recent findings of low Recent findings of low dopamine and DATdopamine and DATRecent findings of Recent findings of persisting hypoactivationpersisting hypoactivation
A range of presentations: MatteoA range of presentations: Matteo
Matteo is regarded by his parents as a charming 8-year-old who has recovered from injury but is now encountering bullying. His teachers, however, refer him to the clinic with a very different story: he does not listen to them, he does not concentrate as he should, he has low academic self-esteem and big tempers when frustrated, he is inclined to lose his way, he is clumsy and his handwriting is terrible.
He was popular when he started at school, but now is teased a great deal. His teachers are frustrated because in individual sessions he shows good understanding and creativeness.
A complex disorder, multiply causedA complex disorder, multiply caused
Inattention creates an increasingly unstimulating environment
Effect sizes on ADHD scalesEffect sizes on ADHD scales
0
0.2
0.4
0.6
0.8
1
1.2
MPH- IR Concerta Equasym ATOMOX
Parent effectTeacher effect
Psychological interventionsPsychological interventions
Type Delivery Costed as:
Parent training Group
Individual
Group + child
10 sessions
10 sessions
Cognitive Individual n/a [no effect]
Educational Class information
Screening
Delivery to teacher
n/a
Principles of psychological treatmentPrinciples of psychological treatment Identify specific problems Analyse contingencies Enhance adult attending Teach effective instruction Token economy + response cost (frequent)
or time-out + rapid novel rewards Include self- management
A school-based trialA school-based trial
Tymms & Merrill (2009)86 schools & 2,584 pupils in randomised trial
Year 2 behaviour in schools receiving an Information Booklet was improved (ES = 0.26)Pupil attitudes to school and reading were improved (ES = 0.17)No effect of screening programme.
Cost of booklet £2.55
(similar booklet in Taylor E (ed) People with Hyperactivity. CDM 171; MacKeith Press)
Learning social skills in peer groupLearning social skills in peer group
Listen to others Join play gradually Learn the rules
Avoid intrusiveness and excessive demands
Figure out why others react Control anger Learn how to refuse kindly
Especially drugs
But do behavioural treatments work? Metaanalysis
But do behavioural treatments work? Metaanalysis
Pelham & Fabiano (2008) review: Behavioural parent training Behavioural classroom management Intensive intervention in recreational settings
Journal of Clinical Child and Adolescent Psychiatry 37 184
Table 5. Databases searched and inclusion/exclusion criteria for clinical evidence
Electronic databases CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO
Date searched Database inception to 18.12.08
Study design RCT
Patient population Children diagnosed with ADHD
Interventions Any non-pharmacological intervention used to treat ADHD symptoms and/or associated behavioural problems
Outcomes ADHD symptoms*; conduct problems*; social skills*; emotional outcomes*; self-efficacy*; reading; mathematics; leaving study early due to any reason, non-response to treatment.
*Separate outcomes for teacher, parent, self, and independent ratings.
NICE approach: Systematic literature review
Cost-effectiveness calculationCost-effectiveness calculation
Table 10. Cost-effectiveness of parent training versus no treatment in children with ADHD - results of the base-case analysis over 1 year
Intervention
Total QALYs / child
Total cost / child ICER
Parent training
0.803 £168 Parent training versus no treatment: £6,608/QALYNo
treatment0.785 0
Sensitivity analyses for differing assumptions
Economic conclusionEconomic conclusion
According to this analysis, and after assuming an 80% uptake of such programmes, the group clinic-based programme resulted in a cost per responder of £10,060 and £1,006 at a 5% and 50% success (response) rate, respectively; and a cost per QALY of £12,575 and £3,144 at a 5% and 20% improvement in HRQoL, respectively.
Clinical conclusionsClinical conclusions
The results of the economic analysis indicate that group-based parent training programmes (or CBT for children of school age) are likely to be cost-effective for children with ADHD, if the mode of delivery of such programmes does not affect their clinical effectiveness. Individual parent training is unlikely to be a cost-effective option
Assessment Points
Baseline EarlyTreatment
(3 m)
Mid-Treatment
(9 m)
End ofTreatment
(14 m)
FirstFollow-up
(24 m)
SecondFollow-up
(36 m)
14-m Treatment
Phase
10-m Follow-up
Phase
22-m Follow-up
Phase
0 362414
Month
RecruitmentScreeningDiagnosis
RANDOM
ASSIGNMENT
579 Subjects7 to 9 yrs old
ADHD-Combined
MedMgt144 Subjects
Beh144 Subjects
Comb 145 Subjects
CC 146 Subjects
Observation 1 LNCG Group
Pre-Baseline
Observation 2 LNCG Group
Comparing Therapies:Conclusions from MTA StudyComparing Therapies:Conclusions from MTA Study
Medication is more powerful than behavioural treatment at 14 months
Research treatment better than routine
Many advantages in adding medicationto behavioural treatment; few in adding behavioural treatment to medication
Comparing therapies:MTA TimelineComparing therapies:MTA Timeline
Study
Treatments
Basel
ine,
7-9
.9 y
rs
8 Yea
rs
6 Yea
rs
36 M
os, 1
0-14
yrs
24 M
os, 9
-12
yrs
14 M
os, 8
-12
yrs
10 Y
ears
Randomisation ends
36 Month Findings on Substance Use
Molina et al
Jensen et al, 2007Intent-to-treat (ITT) Analysis Jensen et al, 2007Intent-to-treat (ITT) Analysis
Randomized Clinical Trial at 14-month assessment: Transition to Naturalistic Follow-up at the 24-month & 36-month Assessment
MTA Group, 1999a,b
MTA Group, 2004a,b
Equifinality of Interventions: How Should Clinical Services React?Equifinality of Interventions: How Should Clinical Services React?
Results underestimate treatment effects?
Treatments lack long-term benefit?
Extra benefits of intensive therapy fade?
Self-selection makes good outcomes
SubtypingSubtyping
ANXIETY / DEPRESSION
HKDHKDHYPHYP3/53/5INATINAT
6/96/9
IMPIMP1/41/4
SCHOOLSCHOOL HOMHOMEE
IMPAIRMENTIMPAIRMENT
ADHD versus HKDADHD versus HKD
ANXIETY / DEPRESSION
HKDHKDHYPHYP3/53/5INATINAT
6/96/9
IMPIMP1/41/4
SCHOOLSCHOOL HOMHOMEE
IMPAIRMENTIMPAIRMENT
SNAP Hyperactivity-Impulsivity (Parent)SNAP Hyperactivity-Impulsivity (Parent)
HYPERKINETIC DISORDER (n=145)
0.60
0.85
1.10
1.35
1.60
1.85
2.10
2.35
D 3 m 9m 14m
ASSESSMENT POINTS
Combined
MedMgt
Psychosocial
Community
ADHD without HYPERKINETIC DISORDER (n=434)
0.60
0.85
1.10
1.35
1.60
1.85
2.10
2.35
D 3m 9m 14m
ASSESSMENT POINTS
Combined
MedMgt
Psychosocial
Community
SNAP Hyperactivity-Impulsivity (Parent)SNAP Hyperactivity-Impulsivity (Parent)
HYPERKINETIC DISORDER (n=145)
0.60
0.85
1.10
1.35
1.60
1.85
2.10
2.35
D 3 m 9m 14m
AS S ES S MENT P OINTS
MedMgt
P sychosocial
ADHD w ithout HYPERKINETIC DISORDER (n=434)
0.60
0.85
1.10
1.35
1.60
1.85
2.10
2.35
D 3m 9m 14m
AS S ES S MENT P OINTS
MedMgt
Psychosocial
HYPERKINETIC DISORDER (n=145)
0.95
1.00
1.05
1.10
1.15
1.20
1.25
1.30
D 3m 9m 14m
ASSESSMENT POINTS
Combined
MedMgt
Psychosocial
Community
ADHD without HYPERKINETIC DISORDER (n=434)
0.95
1.00
1.05
1.10
1.15
1.20
1.25
1.30
D 3m 9m 14m
ASSESSMENT POINTS
Combined
MedMgt
Psychosocial
Community
SSRS Total Social Skills (Parent)SSRS Total Social Skills (Parent)
Economic modellingEconomic modelling
Methylphenidate
Parent training
Continue
MethylphenidateParent training
Continue
QoL £
Severe casesSevere cases
Methylphenidate
Parent training
Continue
MethylphenidateParent training
Continue
Relative effect of medication to behavioural interventions greater in hyperkinetic subtype
Treatment decisionsTreatment decisions
Severe, pervasive, disabling?
Problems at home? Problems at school?
Persistent after treatment?
Comorbid problems?
Home CBT
Liaison+ self-instruction
Medication
?
Key recommendations from NICEKey recommendations from NICE
ADHD should be recognised and referred Comprehensive specialist assessment; impairment req’d
Trusts to set up lead group Adult services to be developed First choice usually group parent training Severe cases go straight to medication First choice medication usually MPH Shared care expected
Drugs or behaviour therapy?Conclusions so farDrugs or behaviour therapy?Conclusions so far Both are effective Both are cost-effective Medication hazards:
Growth suppression (manageable) Hypertension (avoidable with monitoring) Unknown risks to CVS
ADHD is heterogeneous in severity and course
Specific approaches: cognitive therapySpecific approaches: cognitive therapy
Effective for coexistent anxiety/ depressionFor Core ADHD symptoms, little effect:
Learning to STOP AND THINK Recognising and managing anger
Teaching others to be self-controlledTolerating waiting
So far, trial evidence suggests no effect on core ADHD. What are we doing wrong?
Perhaps teaching cognitive control is hard because there are many routes into impaired control/ impulsiveness
Perhaps teaching cognitive control is hard because there are many routes into impaired control/ impulsiveness
Varieties of “inattention”Varieties of “inattention”
Attention domainsAttention domains Executive functionExecutive function AlertingAlerting Sustaining vigilanceSustaining vigilance Resisting distractionResisting distraction Altering focusAltering focus Allocating resourceAllocating resource Modify responsivenessModify responsiveness
Planning
Reaction time,
Continuous performance tests
CPT with distractors
Central-incidental learning
Dual task
“Inhibition”, preparedness, Sternberg, cognitive energetics
A sustained attention deficit?A sustained attention deficit?
02468
1012
Beginning oftask
End of task
% e
rror
s
ADHDControl
Number of errors are high and responses slow throughout the test
eg Sergeant et al 1990
Slowing the presentation rateSlowing the presentation rate
0123456789
2 seconds 8 seconds
% c
omm
issi
on e
rror
s
ADHDControl
Van der Meere et al 1995
A preparation deficit?A preparation deficit?
0
0.2
0.4
0.6
0.8
1
1.2
1 second 15 sec 30 sec
ADHDControl
Warning Signal ResponseRT
Sonuga Barke et al 1993
GONOGOGONOGO STOPSTOP GONOGOGONOGO STOPSTOP
press press inhibitinhibit
Selective inhibition of a Selective inhibition of a motor response/response motor response/response selectionselection
ISI: 1.6spress inhibit
Withholding of a planned motor response
REVERSALREVERSAL
press inhibit
SWITCH TASKSWITCH TASKSWITCH TASKSWITCH TASK
Modification of Meiran Switch task: Cognitive flexibility. Switching between two dimensions.
Delay of gratificationDelay of gratification
Useful clinical test in preschool children; needs to be subtler for older children (Mischel).
Delay aversion v inhibitionDelay aversion v inhibition
Evidence for both; inhibitory failure in more severe cases
Combination of both predicts behavior much more strongly than either alone (Solanto et al)
Inhibition (5-choice serial RT; 5HT2A,C) and preference for delayed reward (5HT2C,B) show double dissociation with 5-HT receptor (Talpos et al)
Time scales of reward effectsTime scales of reward effects
Response to reward
Anticipation Effects
Choice between alternatives
Expectation
Previous reward historyReinforcement schedules
Pairing
Rapid change of activity
‘Reward’ Problems presented in psychopathology‘Reward’ Problems presented in psychopathology Misbehaviour (“oppositional/conduct disorders”) Anhedonia Misery Addiction Hunger for novelty/sensation/reward/dopamine Apparently dysfunctional choices (risky or
punished activities) Insensitivity to reward schedules
Clinicians use of reward mechanismsClinicians use of reward mechanisms Parent Training
Clarity, consistency, speed
Premack principle Reward schedules
enuresis training reward frequency before training
Reward novelty [Density, predictability, reward/punishment ratios]
Clinicians’ use of punishment mechanismsClinicians’ use of punishment mechanisms Reduction of naturalistic punishment Response cost (Time-out)
Conceptualised as extinction
What is it like to be inattentive/ impulsive?What is it like to be inattentive/ impulsive?
““My thoughts are in a muddle”My thoughts are in a muddle” (usually only after treatment shows the difference)(usually only after treatment shows the difference)
““I get into trouble a lot, I don’t know why”I get into trouble a lot, I don’t know why” ““Other kids pick on me”Other kids pick on me” ““Ive got a bad temper”, “I cant concentrate”, “Ive Ive got a bad temper”, “I cant concentrate”, “Ive
got ADHD” got ADHD” (usually repeating what they have been told)(usually repeating what they have been told)
ConclusionsConclusions
There are several testable cognitive dysfunctionsThere are several testable cognitive dysfunctions Response organisation, switching, reward, timingResponse organisation, switching, reward, timing
They are found in several presentationsThey are found in several presentations Attention deficit, impulsiveness, irritabilityAttention deficit, impulsiveness, irritability
Useful for individual analysis, not diagnosisUseful for individual analysis, not diagnosis But most tests are unstandardisedBut most tests are unstandardised
Could help to guide teaching Could help to guide teaching Treatment does not usually depend on causeTreatment does not usually depend on cause
Consider behaviour modification and medicationConsider behaviour modification and medication
Research knowledge on ADHDResearch knowledge on ADHD
Common, persistent, risk for mental health Neurobiology becoming clearer
Low dopamine levels in striatum (PET) Frontostriatal (& other) brain changes (MRI) Genetic and environmental causes
• Allelic variants associated, esp genes in dopamine system
Effective treatments Stimulants, atomoxetine, behaviour therapy Efficacy is not related to cause
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