Attention Deficit/ Hyperactivity Disorder (AD/HD): Dr. Elizabeth Sheppard

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Attention Deficit/ Hyperactivity Disorder
(AD/HD)Dr. Elizabeth Sheppard
Developmental Cognitive Neuropsychology (C8CLDC)
Child Clinical Neuropsychology (C8DCHN)
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Objectives

• Learn about diagnostic/ behavioural features of
  ADHD
• Discuss cognitive explanations of ADHD as a
  disorder of EF
• Discuss abnormalities in brain structure and
  function in ADHD
• Think about question of discriminant validity
  if autism ADHD are both executive disorders

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Diagnostic Criteria
2 groups of symptoms types A) Inattention - makes
careless mistakes in schoolwork, or other
activities difficulty sustaining attention in
tasks or play activities does not seem to listen
when spoken to directly does not follow through
on instructions has difficulty organising tasks
and activities avoids, dislikes, or is reluctant
to engage in tasks that require sustained mental
effort loses things necessary for tasks or
activities easily distracted by extraneous
stimuli forgetful
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Diagnostic Criteria
Bi) Hyperactivity - fidgets with hands or feet or
squirms in seat leaves seat in situations in
which remaining in seat is expected runs about
or climbs excessively in situations in which it
is inappropriate difficulty playing or engaging
in leisure activities quietly talks
excessively Bii) Impulsivity - blurts out
answers before questions have been
completed difficulty awaiting turn
interrupts or intrudes on others (e.g.,
butts into conversations)
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Diagnostic Criteria

• Additional features
• Symptoms are developmentally inappropriate and
  persist for 6 months or longer
• Age of onset around 3-4yrs (Palfrey et al., 1985)
• Symptoms are exhibited in two or more settings
  (e.g., at school or at home)
• Prevalence 1-7 (Hinshaw, 1994)
• Males more likely to be affected ratio of at
  least 31 (Szatmari et al., 1989)

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Diagnostic Criteria

• In Summary

B. Hyperactivity / Impulsivity
A. Inattention
AD/HD Inattentive Type 27
AD/HD Hyperactive Type 18
AD/HD Combined Type 55
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Evidence for ED in ADHD

• Evidence for Executive dysfunction in ADHD comes
  from
• Cognitive studies are individuals with ADHD
  impaired on cognitive tasks of EF?
• Biological studies which areas of brain are
  implicated in ADHD?

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Core Cognitive Difficulties

• Behavioural Inhibition Deficit Barkley, 1997

• Behavioural Inhibition
• e.g., Ability to inhibit a prepotent response

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Core Cognitive Difficulties?

• Behavioural Inhibition Deficits Tested with
  tasks requiring control of actions, e.g., the
  Go/No-go Task (Ozonoff et al., 1994)

Say Go to all Squares, but not to Circles
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Core Cognitive Difficulties?

• Behavioural Inhibition Deficits Tested with
  tasks requiring control of actions, e.g., the
  Go/No-go Task

Time
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Core Cognitive Difficulties?

• Behavioural Inhibition Deficits Tested with
  tasks requiring control of actions, e.g., the
  Stop Signal Task (Ozonoff Strayer, 1997)

Say Go to all Pokemons and No-go to Meowth,
but stop and say nothing when you see the Stop
sign!
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Core Cognitive Difficulties?

• Behavioural Inhibition Deficits Tested with
  tasks requiring control of actions, e.g., the
  Stop Signal Task

Time
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Core Cognitive Difficulties?

• Behavioural Inhibition Deficits Tested with
  tasks requiring control of actions, e.g., the
  Go-Nogo Task, or the Stop Signal Task Logan et
  al., 1984

Stop!
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Core Cognitive Difficulties?

• Review Pennington Ozonoff (1996)
• reviewed studies that presented EF tasks to those
  with ADHD
• 15/18 studies found a significant difference
  between those with ADHD and comparison
  participants on one or more measures of Exec
  Function.
• Found those with ADHD poorer than comparison
  participants 40/60 (67) tasks used across
  studies.

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Biological evidence

• Differences in size of structures involved in
  control of action e.g., reviewed in Swanson et
  al., 1998

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Brain Structure

• Differences in size of structures involved in
  control of action Caudate e.g., Castellanos et
  al., 2003

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Brain Function

• Differences in activity for control-related
  circuits e.g., Durston et al., 2003

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Brain Function

• Lou et al. (1984) found decreased blood flow to
  frontal lobes in ADHD children
• Zametkin et al. (1990) found an overall reduction
  in cerebral glucose utilisation, especially in
  right frontal areas of parents of ADHD children
• Methylphenidate (Ritalin) as treatment of choice
  (or similar pharmacological agents), effects on
  control-related processes e.g., Aron et al.,
  2003

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Brain Function
Methylphenidate (Ritalin) as treatment of choice
(or similar pharmacological agents) normalises
baseline differences in blood flow Lee et al.,
2005
IMPORTANT Need for combined treatment approaches
MTA Cooperative Group, 1999
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Genetics

• Greater frequency of high-risk variants of
  genes related to functions of key
  neurotransmitters (dopamine) (Swanson
• et al., 2000)
• Dopamine Transporter (DAT-1)
• Dopamine Receptor (DRD4)

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Gene Cognition Interactions

• Cognitive Level
• e.g., Differences in inhibitory skills relate to
  DRD4 polymorphism e.g., Langley et al., 2004

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Gene Brain Interactions
Brain Level (Structure) e.g., Differences in
polymorphisms are reflected in structural
differences across the brain DAT1 genotype ?
caudate volume DRD4 genotype ? prefrontal volume
Durston et al., 2005
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Interactions - Gene/Environment

• There are important interactions between genotype
  and environmental variables
• Early-onset antisocial behaviour in AD/HD is
  predicted by a specific genetic variant
  previously linked with prefrontal cortical
  function and birth weight
• Those possessing the high-risk genotype are more
  susceptible to the adverse effects of prenatal
  risk as indexed by lower birth weight Langley
  Thapar, 2006

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Interim summary

• Evidence supports notion of ADHD as a disorder of
  executive function
• Cognitive evidence poor performance on tests of
  inhibition
• Biological evidence frontal lobes implicated
• But issue of discriminant validity how can
  symptomatically different disorders (autism
  ADHD) stem from the same underlying cause?

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How can the DV problem be solved?

• Biological level
• Pennington Ozonoff (1996) argue 6 possible
  biological explanations
• 1.) Differences in severity e.g. differing
  levels of dopamine depletion
• 2.) Time in development when insult occurs but
  all present early in life
• 3.) Different single brain changes within the PFC
  i.e. different parts altered but general family
  resemblance between symptoms

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How can the DV problem be solved?

• 4.) Changes in brain outside but related to PFC
  Weinberger (1992) distinguishes intrinsic
  extrinsic frontal disorders neuropathology
  outside PFC can cause dysfunction within PFC as
  part of complex system e.g. basal ganglia in ADHD
• 5.) 2 localised changes in brain development
  one in PFC (? ED) and one outside (? behavioural
  effects)
• 6.) Diffuse changes in the brain i.e. a general
  change in brain development e.g. neuronal number,
  structure, connectivity. EFs may be vulnerable to
  such changes due to complexity

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How can the DV problem be solved?

• Cognitive level
• It may be that different disorders are deficient
  in differing EFs or have different profiles of ED
  severity at cognitive level
• Some early studies on autism informative as have
  ADHD as comparison group
• Szatmari et al. (1990) - 80 of the comparison
  sample met criteria for ADHD and/or conduct order
  - also associated with impairments in EF. Those
  with autism made significantly more errors on the
  WCST
• Ozonoff et al. (1991) children with autism were
  impaired on WCST and especially the Tower of
  Hanoi in relation to comparison participants 25
  of whom had a diagnosis of ADHD.

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How can the DV problem be solved?

• Ozonoff Jensen (1999) examined EF profiles in
  groups of children with ASD, Tourette Syndrome,
  ADHD and typically developing (TD) comparison
  participants
• Tested on Tower of Hanoi (planning) WCST (mental
  flexibility) Stroop task (inhibition)
• On Tower of Hanoi WCST the group with ASD sig.
  poorer than all other groups (no diff between
  other groups)
• On Stroop task, ADHD group only were sig. poorer
  than TD group
• Conclude disorders can be differentiated on basis
  of exec profiles double dissociation

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How can the DV problem be solved?

• Geurts et al. (2004) compare groups with autism,
  ADHD TD on various tasks including stop signal
  task, self-ordered pointing, Tower of London,
  WCST, verbal fluency
• Group with ASD showed deficits in inhibition,
  planning, fluency, cognitive flexibility but not
  working memory
• Those with ADHD showed problems with verbal
  fluency inhibition only
• Conclude those with autism show more generalised
  EF problems than ADHD no double dissociation!

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How can the DV problem be solved?

• Goldberg et al. (2005) compare groups with
  autism,
• ADHD TD on measures of inhibition,
  planning, mental
• flexibility working memory

• Only group differences were on working memory
  task (form of self-ordered pointing)
• Participants with autism made more errors than TD
  group for 8 items 6 items Those with ADHD made
  more errors for 8 items only
• Conclude working memory impaired in those with
  autism ADHD but more severe in autism

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How can the DV problem be solved?

• Some argue autism has additional cognitive
  features not related to ED e.g. weak central
  coherence
• Booth et al. (2003) drawing task
• Planning making changes to accommodate new
  feature
• WCC drawings rated for strategy, fragmentation
  configural violations
• Autism ADHD showed planning deficits in
  comparison to TD
• Only autism group showed WCC
• Conclude WCC specific to autism

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Summary

• Autism ADHD both involve ED
• Differences may arise from
• Cognitive
• Which EFs affected
• Severity of impairment
• Additional deficits such as WCC
• Biological
• Exact location of damage
• Extent of damage
• Damage to other regions
• Further research needed to establish profiles of
  impairment in different developmental disorders

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References

• Aron, A. R., Dowson, J. H., Sahakian, B. J.,
  Robbins, T. W. Methylphenidate improves response
  inhibition in adults with attention-deficit/hypera
  ctivity disorder. Biological Psychiatry, 54,
  1465-1468.
• Barkley, R. A. (1997). Behavioral inhibition,
  sustained attention, and executive functions
  Constructing a unifying theory of ADHD.
  Psychological Bulletin, 121, 65-94.
• Booth, R., Charlton, R., Hughes, C., Happé
  (2003). Disentangling weak coherence and
  executive dysfunction planning drawing in autism
  and attention-deficit/hyperactivity disorder.
  Philosophical Transactions of the Royal Society
  of London, B, 385, 387-392.
• Castellanos, F. X., Sharp, W. S., Gottesman, R.
  F., Greenstein, D. K., Giedd, J. N., Rapoport,
  J. L. (2003). Anatomic Brain Abnormalities in
  Monozygotic Twins Discordant for Attention
  Deficit Hyperactivity Disorder. American Journal
  of Psychiatry, 160, 1693-1695.
• Durston , S., Fossella, J. A., Casey, B. J., Pol,
  H. E., Galvan, A., Schnack, H. G., Steenhuis, M.
  P., Mindera, R. B., Buitelaar, J. K., Kahn, R.
  S., van Engeland, H. (2005). Differential
  effects of DRD4 and DAT1 genotype on
  fronto-striatal grey matter volumes in a sample
  of subjects with ADHD, their unaffected siblings
  and controls. Molecular Psychiatry, 10, 678-685.
• Durston, S., Tottenham, N. T., Thomas, K. M.,
  Davidson, M. C., Eigsti, I.-M., Yang, Y., Ulug,
  A. M., Casey, B. J. (2003). Differential
  patterns of striatal activation in young children
  with and without ADHD. Biological Psychiatry, 53,
  871-878.
• Goldberg, M. C., Mostofsky, S. H., Cutting, L.
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  Landa, R. J. (2005). Subtle executive
  impairment in children with autism and children
  with ADHD. Journal of Autism and Developmental
  Disorders, 35, 279-293.
• Guerts, H. M., Verté, S., Oosterlaan, J.,
  Roeyers, H., Sergeant, J. A. (2004). How
  specific are executive functioning deficits in
  attention deficit hyperactivity disorder and
  autism? Journal of Child Psychology and
  Psychiatry, 45, 836-854.

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References

• Hinshaw, S. P. (1994). Attention deficits and
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• Langley, K., Marshall, L., van der Bree, M.,
  Thomas, H., Owen, M., ODonovan, M., Thapar, A.
  (2004). Association of the dopamine D4 receptor
  gene 7-repeat allele with neuropsychological test
  performance of children with ADHD. American
  Journal of Psychiatry, 161, 133-138.
• Langley, K., Thapar, A. (2006) COMT Gene
  Variant and Birth Weight Predict Early-onset
  Antisocial Behavior in Children with Attention
  Deficit Hyperactivity Disorder. Directions in
  Psychiatry, 26, 219-225.
• Lee, J. S., Kim, B. N., Kang, E., Lee, D. S.,
  Kim, Y. K., Chung, J-K, Lee, M. C., Cho, S. C.
  (2005). Regional Cerebral Blood Flow in Children
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• Logan, G. D., Cowan, W. B., Davis, K. A. (1984).
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• Ozonoff, S., Jensen, J. (1999). Brief report
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• Ozonoff, S., Pennington, B. F., Rogers, S. J.
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• Ozonoff, S., Strayer, D. L. (1997). Inhibitory
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