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

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

2. 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

3. 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

4. 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)

5. 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 3:1 (Szatmari et al., 1989)

6. In Summary: Diagnostic Criteria B. Hyperactivity / Impulsivity A. Inattention AD/HD – Inattentive Type [27 %] AD/HD – Combined Type [55 %] AD/HD – Hyperactive Type [18%]

7. 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?

8. Self – regulation: • e.g., emotional self-control • Speech Internalization: • e.g., description and reflection • Reconstitution • e.g., analysis and synthesis of behaviour • Working Memory: • e.g., acting on events held in memory Core Cognitive Difficulties • Behavioural Inhibition Deficit [Barkley, 1997] • Behavioural Inhibition: • e.g., Ability to inhibit a prepotent response

9. 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

10. Core Cognitive Difficulties? • Behavioural Inhibition Deficits: Tested with tasks requiring control of actions, e.g., the Go/No-go Task: Time

11. 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!

12. Core Cognitive Difficulties? • Behavioural Inhibition Deficits: Tested with tasks requiring control of actions, e.g., the Stop Signal Task: Time

13. 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!

14. 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.

15. Differences in size of structures involved in control of action [e.g., reviewed in Swanson et al., 1998] Biological evidence

16. Differences in size of structures involved in control of action: Caudate [e.g., Castellanos et al., 2003] Brain Structure

17. Differences in activity for control-related circuits [e.g., Durston et al., 2003] Brain Function

18. 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]

19. 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]

20. 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) Genetics

21. Gene – Cognition Interactions Cognitive Level: e.g., Differences in inhibitory skills relate to DRD4 polymorphism [e.g., Langley et al., 2004]

22. 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]

23. 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]

24. 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?

25. 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

26. 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

27. 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.

28. 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

29. 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!

30. 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

31. 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

32. 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

33. References • Aron, A. R., Dowson, J. H., Sahakian, B. J., & Robbins, T. W. Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity 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. E., Mahone, E. M., Astor, B. C., Denckla, M. B., & 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.

34. References • Hinshaw, S. P. (1994). Attention deficits and hyperactivity in children. London: Sage. • Langley, K., Marshall, L., van der Bree, M., Thomas, H., Owen, M., O’Donovan, 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 With Attention Deficit Hyperactivity Disorder: Comparison Before and After Methylphenidate Treatment. Human BrainMapping, 24, 157-164. • Logan, G. D., Cowan, W. B.,& Davis, K. A. (1984). On the ability to inhibit simple and choice reaction time responses: A model and a method.Journal of Experimental Psychology: Human Perception and Performance, 10,276-291. • Lou, H. C., Henricksen, L., & Bruhn, P. (1984). Focal cerebral hypoperfusion in children with dysphasia and/or attention deficit disorder. Archives of Neurology, 41, 825-829. • Ozonoff, S., & Jensen, J. (1999). Brief report: Specific executive function profiles in three neurodevelopmental disorders. Journal of Autism and Developmental Disorders, 29, 171-177. • Ozonoff, S., Pennington, B. F., & Rogers, S. J. (1991). Executive function deficits in high-functioning autistic individuals: Relationship to theory of mind. Journal of Child Psychology and Psychiatry, 32, 1081-1105. • Ozonoff, S., & Strayer, D. L. (1997). Inhibitory function in nonretarded children with autism. Journal of Autism and Developmental Disorders, 27, 59-77.

35. References • Ozonoff, S., Strayer, D. L., McMahon, W. M., & Filloux, F. (1994). Executive function abilities in autism: An information processing approach. Journal of Child Psychology and Psychiatry, 35, 1015-1031. • Palfrey, J. S., Levine, M. D., Walker, D. K., & Sullivan, M. (1985). The emergence of attention deficits in early childhood: A prospective study. Journal of Developmental and Behavioral Pediatrics, 6, 339-348. • Pennington, B. F., & Ozonoff, S. (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry, 37, 51-87. • Swanson, J., Castellanos, F. X., Murias, M., LaHoste, G., & Kennedy, J. (1998). Cognitive neuroscience of attention deficit hyperactivity disorder and hyperkinetic disorder. Current Opionion in Neurobiology, 8, 263-271. • Swanson, J. M., Flodman, P., Kennedy, J., Spence, M. A., Moyzis, R., Schuck, S., Murias, M., Moriarity, J., Barr, C., Smith, M., & Posner, M. (2000). Dopamine genes and ADHD. Neuroscience and Biobehavioral Reviews, 24, 21-25. • Szatmari, P., Offord, D. R., & Boyle, M. (1989). Correlates, associated impairments, and patterns of service utilization of children with attention deficit disorders: findings from the Ontario Child Health Study. Journal of Child Psychology and Psychiatry, 30, 205-217. • Szatmari, P., Tuff, L., Finlayson, M. A. J., & Bartolucci, G. (1990). Asperger’s syndrome and autism: Neurocognitive aspects. Journal of the American Academy of Child and Adolescent Psychiatry, 29, 130-136. • Weinberger, D. R. (1992). A Neural Systems Approach to the Frontal Lobes. Presented at the American Academy of Neurology, San Diego. • Zametkin, A. J., Nordahl, T. E., Gross, M., King, A. C., Semple, W. E., Rumsey, J., Hamburger, S., & Cohen, R. (1990). Cerebral glucose metabolism in adults with hyperactivity of childhood onset. New England Journal of Medicine, 323, 1361-1366.