ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.
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Transcript of ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.
![Page 1: ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.](https://reader035.fdocuments.us/reader035/viewer/2022062518/56649e865503460f94b88ab8/html5/thumbnails/1.jpg)
ADHDIN
CHILDHOOD
Highlights in Psychiatry, 2007
Marina Danckaerts, UPC-K.U.Leuven
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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
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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
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• 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
Neuroscience-neuropsychology-behaviourCasey ea 2007, Curr Opin Neurol; Swanson ea 2007, Neuropsychol Rev
MRI and fMRI studies systematically show abnormalities
in prefrontal cx, n.caudatus, cerebellum & parietal cx
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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.
Neuroscience-neuropsychology-behaviourDevelopment
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Neuroscience-neuropsychology-behaviour
Development
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
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Neuroscience-neuropsychology-behaviourDevelopmental theories
• Model: dopamine reinforcement learningCasey ea 2007, Curr Opin Neurol; Tripp & Wickens 2007, Eunethydis Meeting
Normal development ADHD
Learning to “expect” Reward dependent
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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
![Page 9: ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.](https://reader035.fdocuments.us/reader035/viewer/2022062518/56649e865503460f94b88ab8/html5/thumbnails/9.jpg)
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
Li ea 2006, Hum Mol Genet
Nigg ea 2007, Biol. Psychiatry
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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)
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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
![Page 12: ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.](https://reader035.fdocuments.us/reader035/viewer/2022062518/56649e865503460f94b88ab8/html5/thumbnails/12.jpg)
ADHD Treatment Guidelines
• 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)
• 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)
EU GuidelinesEU Guidelines US GuidelinesUS Guidelines
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Treatment Guidelines
• Growing armamentarium
• More evidence based
• Growing literature on side-effects
• Choice stimulants and non-stimulant
Effect size 10% larger
Full effect after days
Lower cost
Effect gradual over weeks
Long-lasting effect
May be preferred in comorbid cases with tics, anxiety, risk of substance abuseSpencer ea 2007, Geller ea 2007,
Kelsey ea 2007, ESCAP Posters
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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
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• 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
Medication Side-effects/Safety
Conclusion: closer monitoring
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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
![Page 17: ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.](https://reader035.fdocuments.us/reader035/viewer/2022062518/56649e865503460f94b88ab8/html5/thumbnails/17.jpg)
MTA: NIMH landmark study
EarlyTreatment
(3 m)
Mid-treatment
(9 m)
EndTreatment
(14 m)
Follow-up(24 m)
14-m Treatment Stage
10-m Follow-up After
Treatment
22-m Follow-up After
Treatment
0 362414Month
RandomAssignment
579 ADHD Subjects
Medication Only144 Subjects
Psychosocial (Behavioral)Treatment Only
144 Subjects
Combined Medication & Behavioral Treatment
145 Subjects
Community ControlsNo Treatment from Study
146 Subjects
Recruitment of LNCG Cohort
36 m FU
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0
0,5
1
1,5
2
2,5
3
0 100 200 300 400
CC
Beh
MedMgt
Comb
Time x Tx: F=10.6, p<.0001Site x Tx: F=0.9, nsSite: F=2.7, p<.02
Comb, MedMgt > Beh, CC
Ave
rag
e S
core
Assessment Point (Days)
MTA: 14-month outcomeTeacher SNAP-Inattention
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MTA: 36 month Follow-Up
Initial treatment does not seem to make a difference.
All did better.
Continuous Med (> 50% of days) versus non-continuous Med : no difference
Stop study Tr.
Influential study, but hard to interpret at this point in time !
Jensen ea 2007
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Outcome research
ADHD + CD Controls OR *p<.001
Arrests 44% 15% 4.57*
Convictions 29% 8% 4.68*
Incarcerations 26% 8% 4.08*
All children had 3y.multimodal treatment between 6-12y
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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)
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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
![Page 23: ADHD IN CHILDHOOD Highlights in Psychiatry, 2007 Marina Danckaerts, UPC-K.U.Leuven.](https://reader035.fdocuments.us/reader035/viewer/2022062518/56649e865503460f94b88ab8/html5/thumbnails/23.jpg)
Psychosocial treatmentParent Management Training
• 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
Pelham ea, in press; VandenOord ea, in press; Jones ea 2007;
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Other therapies
• EEG-biofeedback (Hirschberg, 2007)
• Food supplements (Johnson ea 2007)
• Cognitive rehabilitation
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Conclusions
Genes/Environment
Neuro-anatomy/ Brain development
Neurophysiology/Neuropsychology
Behaviour
Treatment
Outcome