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ADHD IN CHILDHOOD. Marina Danckaerts, UPC-K.U.Leuven. Highlights in Psychiatry, 2007. Disclosure. Have served in Advisory Boards of Cephalon, Janssen, Lilly, Medice, Novartis, Pfizer, UCB Have received support for public speaking from Astra-Zeneca, Janssen, Lilly, Novartis, UCB

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Adhd in childhood

ADHDINCHILDHOOD

Marina Danckaerts, UPC-K.U.Leuven

Highlights in Psychiatry, 2007


Disclosure
Disclosure

  • Have served in Advisory Boards of Cephalon, Janssen, Lilly, Medice, Novartis, Pfizer, UCB

  • Have received support for public speaking from Astra-Zeneca, Janssen, Lilly, Novartis, UCB

  • Have received research support from Janssen, Lilly


Highlights in adhd research in childhood and adolescence
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term treatment outcome

  • Early psychosocial treatment

  • Other treatments


Neur oscience neuropsychology behaviour
Neuroscience-neuropsychology-behaviour

Casey ea 2007, Curr Opin Neurol; Swanson ea 2007, Neuropsychol Rev

  • ADHD = disorder of self-control

  • Prefrontal cortex is central in regulating behaviour (top-down), but subcortical and posterior systems are critical in signaling this system to engage (bottom-up)

  • Control functions may function well when they are “on-line”, but may not be brought on-line when needed

  • Most puzzling:

    • variability in performance

    • heterogeneous findings

MRI and fMRI studies systematically show abnormalities in prefrontal cx, n.caudatus, cerebellum & parietal cx


Neur oscience neuropsychology behaviour development
Neuroscience-neuropsychology-behaviourDevelopment

Increased long-range and decreased short range connectivity with age

Fair et al., 2007

Delay or interruption in these developmental processes might be associated with cognitive deficits in ADHD.


Neur oscience neuropsychology behaviour development1
Neuroscience-neuropsychology-behaviourDevelopment

Possession of the DRD4 7-repeat allele was associated with a thinner right orbitofrontal/inferior prefrontal and posterior parietal cortex.

Participants with ADHD carrying the DRD4 7-repeat allele had a better clinical outcome and a distinct trajectory of cortical development with normalization of the right parietal cortical region.

Shaw ea 2007, Arch Gen Psychiatry


Neur o science neuropsychology behaviour developmental theories
Neuroscience-neuropsychology-behaviourDevelopmental theories

Casey ea 2007, Curr Opin Neurol; Tripp & Wickens 2007, Eunethydis Meeting

  • Model: dopamine reinforcement learning

ADHD

Normal development

Learning to “expect”

Reward dependent


Highlights in adhd research in childhood and adolescence1
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term treatment outcome

  • Early psychosocial treatment

  • Other treatments


Genes environment

Heritability 0.6-0.9

Meta-analysis:

DRD4: 7-repeat allele ~ ADHD

DAT1: less reliable association

Prenatal smoking, alcohol

Family adversity

Low birth weight, prematurity

Low-level Lead exposure

Genes / Environment

Li ea 2006, Hum Mol Genet

Nigg ea 2007, Biol. Psychiatry


Gene environment interactions
Gene-environment interactions

  • Genotype as a resilience factor in the presence of psychosocial adversity (Nigg ea 2007)

  • DAT1 only associated with ADHD in those exposed to prenatal smoking (Kahn ea 2003; not confirmed by Langley ea 2007)

  • Stronger association with DAT1 when mother consumed alcohol during pregnancy (Brookes ea 2006)

  • DRD2 x marital status interaction (Waldman, 2007)


Highlights in adhd research in childhood and adolescence2
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term treatment outcome

  • Early psychosocial treatment

  • Other treatments


Adhd in childhood

ADHD Treatment Guidelines

EU Guidelines

US Guidelines

  • 1997: AACAP (American Academy of Child and Adolescent Psychiatry, J Am Acad Child Adolesc Psychiatry 1997)

  • 2000: Texas Children’s Medication Algorithm

    (Pliszka GR et al. J Am Acad Child Adolesc Psychiatry 2000)

  • 2000: NIH (National Institute of Health, J Am Acad Child Adolesc Psychiatry, 2000)

  • 2001: AAP (American Academy of Pediatrics, Pediatrics 2000)

  • 2006: Revision of Texas Children’s medication Algorithm

    (Pliszka GR et al. J Am Acad Child Adolesc Psychiatry 2006)

  • 2007: AACAP(American Academy of Child and Adolescent Psychiatry, J Am Acad Child Adolesc Psychiatry)

  • 1998: Clinical Guidelines for hyperkinetic disorder

    (Taylor E et al.Eur Child Adolesc Psychiatry 1998)

  • 2004: European Clinical Guidelines for hyperkinetic disorder – first upgrade

    (Taylor E et al.Eur Child Adolesc Psychiatry 2004)

  • 2006: NICE guidelines (www.NICE.org.uk)

  • 2006: Long-acting medications for the hyperkinetic disorders – a systematic review and European treatment guideline

    (Banaschewski T et al.Eur Child Adolesc Psychiatry 2006)


Treatment guidelines
Treatment Guidelines

  • Growing armamentarium

  • More evidence based

  • Growing literature on side-effects

  • Choice stimulants and non-stimulant

Effect gradual over weeks

Long-lasting effect

May be preferred in comorbid cases with tics, anxiety, risk of substance abuse

Effect size 10% larger

Full effect after days

Lower cost

Spencer ea 2007, Geller ea 2007, Kelsey ea 2007, ESCAP Posters


Highlights in adhd research in childhood and adolescence3
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term treatment outcome

  • Early psychosocial treatment

  • Other treatments


Adhd in childhood

Medication Side-effects/Safety

  • 2006: FDA data review adverse events to ADHD medications (Mosholder 2006)

  • 2006: postmarketing safety data review (Gelperin, 2006)

    • Box warning US: Atx: suicidal thinking in 4/1000 versus 0 in placebo

  • 2006: FDA data review on sudden deaths in patients using stimulants (Villalaba, 2006)

    • 20 on amphetamine, 14 on MPH: does not exceed base rate of sudden death in general population

    • Advise: not to be used in children with pre-existing cardio-vascular risk without cardiologist’s advise

Conclusion: closer monitoring


Highlights in adhd research in childhood and adolescence4
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term (treatment) outcome

  • Early psychosocial treatment

  • Other treatments


Mta nimh landmark study
MTA: NIMH landmark study

Month

0

14

24

36

22-m Follow-

up After

Treatment

10-m Follow-

up After

Treatment

14-m Treatment Stage

Medication Only

144 Subjects

Random

Assignment

Psychosocial (Behavioral)

Treatment Only

144 Subjects

Combined Medication &

Behavioral Treatment

145 Subjects

579 ADHD

Subjects

Community Controls

No Treatment from Study

146 Subjects

Follow-up

(24 m)

Mid-

treatment

(9 m)

End

Treatment

(14 m)

36 m FU

Early

Treatment

(3 m)

Recruitment of

LNCG Cohort


Mta 14 month outcome
MTA: 14-month outcome

Teacher SNAP-Inattention

Average Score

Assessment Point (Days)


Mta 36 month follow up
MTA: 36 month Follow-Up

Influential study, but hard to interpret at this point in time !

Stop study Tr.

Initial treatment does not seem to make a difference.

All did better.

Continuous Med (> 50% of days) versus non-continuous Med : no difference

Jensen ea 2007


Outcome research
Outcome research

All children had 3y.multimodal treatment between 6-12y


Preschool identification poor outcome
Preschool identificationPoor outcome

At 11-13y and 12-14y, fewer children with preschool ADHD were well-adjusted (17,7%) than controls (71.4%)

Medication works less well in preschoolers: PATS-study: 21% normalized with medication, 13% with placebo (Daley, 2007, Eunethydis)


Highlights in adhd research in childhood and adolescence5
Highlights in ADHD research in childhood and adolescence

  • Linking neuroscience to neuropsychology and to behaviour

  • Gene-environment interactions

  • Treatment guidelines

  • Medication side-effects

  • Long term treatment outcome

  • Early psychosocial treatment

  • Other treatments


Adhd in childhood

Psychosocial treatmentParent Management Training

Pelham ea, in press; VandenOord ea, in press; Jones ea 2007;

  • New Forest Parent Training for preschool ADHD children (UK)

  • Positive Parenting Plan (Triple P- US)

  • Incredible Years (UK)

    All work (3-P somewhat less), so far no external validation (only parent ratings)

    Self-administration packages


Other therapies
Other therapies

  • EEG-biofeedback (Hirschberg, 2007)

  • Food supplements (Johnson ea 2007)

  • Cognitive rehabilitation


Conclusions
Conclusions

Genes/Environment

Neuro-anatomy/ Brain development

Neurophysiology/Neuropsychology

Behaviour

Treatment

Outcome