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Working with difficult children: Recent advances in ADHD. Eric Taylor King’s College London Institute of Psychiatry.

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Working with difficult children recent advances in adhd l.jpg

Working with difficult children: Recent advances in ADHD

Eric Taylor

King’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.


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Lessons from research

  • It’s not their fault

  • Psychological treatments work

  • Medicines help the worst affected

  • Increasing range of medicines


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More ‘diagnoses’ for child troubles

Born mad or made bad? Crime and the child

BBC to apologise for child drug program


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Genetic influences 80%;

Frontal, striatal, cerebellar parts of brain are small

Same structures underactivate

Psychological deficits

Great differences over time

Great differences in prevalence between countries

Emotional & behavioural problems

Performance variable

Conflicts in understanding ADHD*

Persistent and pervasive abnormalities in : Attention (distractible, forgetful, disorganised); Activity (restless, fidgety) and Impulsiveness (acting without thinking)


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Where does ADHD come from?Twin studies show high heritability

DZ

MZ

Twin

correlations

Median heritability (13 studies) 0.82 (0.52-0.98)


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Search for high-risk alleles

7 (vs 2-5 or 8) copies of 48 bp VNTR on 11p.15.5

  • DRD4

    • metaanalysis p< .00000001

    • Odds ratio (averaged): 1.32

  • DAT1

    • metaanalysis p<.0001

    • Odds ratio (averaged): 1.13

9 vs 10 copies of 40 bp VNTR on 5p15.3

8 candidate genes well established to be associated with ADHD:

mostly affecting dopamine or serotonin neurotransmission


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Geographical variations in the number of repeats of the variable 48-bp sequence in DRD4

Chang et al


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Genome scan identifies a spot on variable 48-bp sequence in DRD4Chr 16: Cadherin 13

  • Cadherins mediate cell adhesion and play a fundamental role in normal development. They participate in the maintenance of proper cell-cell contacts

  • CDH13 also implicated in substance misuse:

    Nicotine dependence

    Substance dependence

  • Plays a role in cell adhesion, cell-cell contacts and cell-migration


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What is inherited? variable 48-bp sequence in DRD4

  • Not ADHD: genetic influences on continuum*

  • Not a unitary trait: influences vary with context

  • Dispositions to react:

    • gene-environment interactions and correlations

      • early physical environmental associations

      • parenting influences on development

      • MAOA multiplies effects of violence, DRD4.7/DAT10 of smoking

*(with possible exception at highest level of severity & possible latent classes)


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Probable environmental associations variable 48-bp sequence in DRD4

Pregnancy

  • nicotine, alcohol, anticonvulsants, cocaine

  • lead, mercury; thyroid, immune rejection

  • stress; infections; toxaemia;APH

    Perinatal

  • low birth weight, O.C.s, perinatal care, [season of birth]

    Infancy

  • attachment problems, neglect, injury

  • socioeconomic adversity, nutrition

    Childhood

  • Course influenced by exclusion, hostility, injury, school


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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?


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Prevalence of disorder in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

ADHD /1000

Real prevalence

Administrative prevalence from local surveys; HKD in approx 105,000 nationally


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Prevalence of disorder in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Same survey method in Hong Kong and East London


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Is it a Social Problem? in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • Does society determine the presence of ADHD?

    • No, shared environment plays little part

  • Does society alter the rate?

    • Only small differences between societies

    • Little increase over time

  • Does society determine what is recognised?

    • Yes, substantial cultural differences


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Is it a Treatable Problem? in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Patterson - OSLC


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Interventions in the classroom in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • Proximity to teacher

  • Managed transitions

  • Pacing & letting off energy

  • Classroom aide

    • operant conditioning

    • peer advice

  • Rule government

  • Clarity of goal & speed of feedback

  • Understanding disorder (eg projects)

  • Monitoring medication

Some common-sense procedures – avoiding distractors and short-chunk learning – don’t yet have trial evidence


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Specific treatments in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • Psychological therapies:Parent training, behaviour mod, social skills

  • Licensed drugs:Methylphenidate, dexamfetamine, atomoxetine

  • Unlicensed drugs:Trial evidence:pemoline, imipramine, clonidine, bupropion, “Adderall”, modafinil, guanfacineAnecdotal: moclobemide, risperidone, sertraline

  • Diet: eliminations and supplements

Include non-specific interventions - education, support, advice


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A range of presentations: Xavier in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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 complex disorder multiply caused l.jpg
A complex disorder, multiply caused in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Not just bad parents: Medication of child reduces parental EE

  • Not just complications:

  • In never-medicated adults:

  • Recent findings of low dopamine and DAT

  • Recent findings of persisting hypoactivation

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)


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A range of presentations: Matteo in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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.


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A complex disorder, multiply caused in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Inattention creates an increasingly unstimulating environment


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Effect sizes on ADHD scales in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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Psychological interventions in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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Principles of psychological treatment in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • 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


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A school-based trial in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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)


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Learning social skills in peer group in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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 l.jpg
But do behavioural treatments work? Metaanalysis in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Pelham & Fabiano (2008) review:

Behavioural parent training

Behavioural classroom management

Intensive intervention in recreational settings

Journal of Clinical Child and Adolescent Psychiatry 37 184


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NICE approach: Systematic literature review in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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Cost-effectiveness calculation in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Sensitivity analyses for differing assumptions


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Economic conclusion in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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.


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Clinical conclusions in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

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


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Neurofeedback trials meta-analysis in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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Month in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

36

0

14

24

10-m

Follow-up

Phase

22-m

Follow-up

Phase

14-m

Treatment

Phase

R

A

N

D

O

M

A

S

S

I

G

N

M

E

N

T

MedMgt

144 Subjects

Recruitment

Screening

Diagnosis

Beh

144 Subjects

579 Subjects

7 to 9 yrs old

ADHD-Combined

Comb

145 Subjects

CC

146 Subjects

End of

Treatment

(14 m)

First

Follow-up

(24 m)

Second

Follow-up

(36 m)

Early

Treatment

(3 m)

Mid-

Treatment

(9 m)

Baseline

Pre-Baseline

Observation 2 LNCG Group

Observation 1 LNCG Group

Assessment Points


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Comparing Therapies: in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?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


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Comparing therapies:MTA Timeline in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

8 Years

6 Years

24 Mos, 9-12 yrs

36 Mos, 10-14 yrs

14 Mos, 8-12 yrs

Baseline, 7-9.9 yrs

10 Years

Study

Treatments

36 Month Findings on Substance Use

Molina et al

Randomisation ends


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Jensen et al, 2007 in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?Intent-to-treat (ITT) Analysis

MTA Group, 1999a,b

MTA Group, 2004a,b

Randomized Clinical Trial at 14-month assessment: Transition to Naturalistic Follow-up at the 24-month & 36-month Assessment


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Equifinality of Interventions: in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?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


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Subtyping in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

ANXIETY / DEPRESSION

IMP

1/4

SCHOOL

HOME

HKD

HYP

3/5

INAT

6/9

IMPAIRMENT


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ADHD versus HKD in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

ANXIETY / DEPRESSION

IMP

1/4

SCHOOL

HOME

HKD

HYP

3/5

INAT

6/9

IMPAIRMENT


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SNAP Hyperactivity-Impulsivity (Parent) in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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SNAP Hyperactivity-Impulsivity (Parent) in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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SSRS Total Social Skills (Parent) in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?


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Economic modelling in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Continue

£

QoL

Methylphenidate

Parent training

Methylphenidate

Parent training

Continue


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Severe cases in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

Continue

Methylphenidate

Parent training

Methylphenidate

Relative effect of medication to behavioural interventions greater in hyperkinetic subtype

Parent training

Continue


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Treatment decisions in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • Severe, pervasive, disabling?

  • Problems at home?

  • Problems at school?

  • Persistent after treatment?

  • Comorbid problems?

Home CBT

?

Liaison

+ self-instruction

Medication


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Key recommendations from NICE in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

  • 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


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Drugs or behaviour therapy? in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?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 therapy l.jpg

    Specific approaches: cognitive therapy in different places? Isn’t it really a social disorder? What about the rise of television and the decline of the family?

    Effective for coexistent anxiety/ depression

    For Core ADHD symptoms, little effect:

    Learning to STOP AND THINK

    Recognising and managing anger

    Teaching others to be self-controlled

    Tolerating waiting

    So far, trial evidence suggests no effect on core ADHD. What are we doing wrong?


    Slide50 l.jpg

    Perhaps teaching cognitive control is hard because there are many routes into impaired control/ impulsiveness


    Varieties of inattention l.jpg

    Attention domains many routes into impaired control/ impulsiveness

    Executive function

    Alerting

    Sustaining vigilance

    Resisting distraction

    Altering focus

    Allocating resource

    Modify responsiveness

    Varieties of “inattention”

    Planning

    Reaction time,

    Continuous performance tests

    CPT with distractors

    Central-incidental learning

    Dual task

    “Inhibition”, preparedness, Sternberg, cognitive energetics


    A continuous performance test l.jpg
    A continuous performance test many routes into impaired control/ impulsiveness

    Press


    A sustained attention deficit l.jpg
    A sustained attention deficit? many routes into impaired control/ impulsiveness

    Number of errors are high and responses slow throughout the test

    eg Sergeant et al 1990


    Slowing the presentation rate l.jpg
    Slowing the presentation rate many routes into impaired control/ impulsiveness

    Van der Meere et al 1995


    A preparation deficit l.jpg
    A preparation deficit? many routes into impaired control/ impulsiveness

    RT

    Warning

    Signal

    Response

    Sonuga Barke et al 1993


    Gonogo stop l.jpg
    GONOGO STOP many routes into impaired control/ impulsiveness

    • press inhibit

    • Selective inhibition of a motor response/response selection

    press inhibit

    ISI: 1.6s

    Withholding of a planned motor

    response

    REVERSAL

    press

    inhibit


    Switch task l.jpg
    SWITCH TASK many routes into impaired control/ impulsiveness

    Modification of Meiran Switch task: Cognitive flexibility. Switching between two dimensions.


    Delay of gratification l.jpg
    Delay of gratification many routes into impaired control/ impulsiveness

    Useful clinical test in preschool children; needs to be subtler for older children (Mischel).


    Post reward delay l.jpg
    Post - reward delay many routes into impaired control/ impulsiveness

    1 p

    1 p

    30 sec

    ?

    ?

    ?

    2 p

    Experiments by Edmund Sonuga-Barke


    Delay aversion v inhibition l.jpg
    Delay aversion v inhibition many routes into impaired control/ impulsiveness

    • 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)


    Slide61 l.jpg

    Reward & Social Influences many routes into impaired control/ impulsiveness


    Time scales of reward effects l.jpg
    Time scales of reward effects many routes into impaired control/ impulsiveness

    Response to reward

    Anticipation Effects

    Choice between alternatives

    Expectation

    Previous reward history

    Reinforcement schedules

    Pairing

    Rapid change of activity


    Rewarded cpt l.jpg
    REWARDED CPT many routes into impaired control/ impulsiveness

    8

    8

    7

    7

    X

    6

    6

    5

    5

    4

    4

    3

    3

    2

    2

    1

    1

    • FMRI: respond to “X” and “O”. ISI: 900ms


    Specific dysfunctions in cd vs adhd l.jpg
    Specific dysfunctions in CD vs ADHD many routes into impaired control/ impulsiveness

    Sustained Attention

    Reward


    Reward problems presented in psychopathology l.jpg
    ‘Reward’ Problems presented in psychopathology many routes into impaired control/ impulsiveness

    • 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 mechanisms l.jpg
    Clinicians use of reward mechanisms many routes into impaired control/ impulsiveness

    • 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 mechanisms l.jpg
    Clinicians’ use of punishment mechanisms many routes into impaired control/ impulsiveness

    • Reduction of naturalistic punishment

    • Response cost

    • (Time-out)

      • Conceptualised as extinction


    What is it like to be inattentive impulsive l.jpg
    What is it like to be inattentive/ impulsive? many routes into impaired control/ impulsiveness

    • “My thoughts are in a muddle”

      • (usually only after treatment shows the difference)

    • “I get into trouble a lot, I don’t know why”

    • “Other kids pick on me”

    • “Ive got a bad temper”, “I cant concentrate”, “Ive got ADHD”

      (usually repeating what they have been told)


    Conclusions l.jpg
    Conclusions many routes into impaired control/ impulsiveness

    • There are several testable cognitive dysfunctions

      • Response organisation, switching, reward, timing

  • They are found in several presentations

    • Attention deficit, impulsiveness, irritability

  • Useful for individual analysis, not diagnosis

    • But most tests are unstandardised

  • Could help to guide teaching

  • Treatment does not usually depend on cause

    • Consider behaviour modification and medication


  • Research knowledge on adhd l.jpg
    Research knowledge on ADHD many routes into impaired control/ impulsiveness

    • 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