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Attention Deficit Hyperactivity Disorder ADHD

Attention Deficit Hyperactivity Disorder ADHD. ADHD. Childhood-onset, severe impairing inattention, overactivity, impulsiveness Clinical variability Highly heritable especially when severe antisocial symptoms present. Current work. Identifying large, rare CNVs

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Attention Deficit Hyperactivity Disorder ADHD

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  1. Attention Deficit Hyperactivity Disorder ADHD

  2. ADHD • Childhood-onset, severe impairing inattention, overactivity, impulsiveness • Clinical variability • Highly heritable especially when severe antisocial symptoms present

  3. Current work • Identifying large, rare CNVs • Identifying common variants-GWAS of 800 • Identifying biological pathways that underlie ADHD • What are the links between biology, genes and clinical variability in ADHD? • How do associated genes exert risk effects on the clinical outcome?

  4. In-house results

  5. Large rare copy number variants in ADHD Williams et al, Lancet Sept 30th

  6. Large rare CNVs in ADHD • Significant overlap of regions implicated in autism and schizophrenia • 16p13.11 duplications OR 13.9 p=0.0008 (95% CI 2.3-82.2)

  7. Questions? • Does clinical variability in presentation index biological heterogeneity? • Can we pick out biologically homogeneous subtypes? • How do our GWAS and CNV findings relate to animal models of ADHD and imaging studies showing affected brain regions?

  8. COMT influencing antisocial behaviour in ADHD

  9. Met/Met Val/Met Val/Val Conduct disorder symptoms among clinic children with ADHD, according to their COMT Val158Met genotype status Conduct disorder symptoms n = 59 130 52 Thapar et al, Archives of General Psychiatry, 2005

  10. Further replication in ALSPAC (OR=2.82, 95% CI: 2.02, 3.94, p<0.001 Greater than 4 CD symptoms) Langley K, Heron J, O’Donovan M, Owen, Thapar A . Archives of General Psychiatry, 2010. .

  11. Mechanisms? COMT Val/val Antisocial behaviour in ADHD

  12. MechanismsResults from ALSPAC Antisocial behaviour Impaired social understanding COMT Langley et al, 2010. Archives of General Psychiatry,

  13. What next? • Detailed cognitive and psychophysiological testing of ADHD children in experimental lab based on COMTVal158Met genotype • What should we be looking at (gene/mutation-wise) that might be important in relation to COMT function and related pathways?

  14. ….Final add on • 3 wave study of psychiatric problems in adolescents who are at high genetic risk, developing a risk prediction tool • Developing a risk prediction tool that is being incorporated into GP software (commercial software company) • Computing/risk prediction expertise?

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