Nature-Nurture Interplay in Aggression and Antisocial Behaviour

1. Nature-Nurture Interplay in Aggression and Antisocial Behaviour Emily Simonoff Institute of Psychiatry London

2. Size of the Problem • Conduct disorders are the most common group of child psychiatric disorders • In the UK, over one quarter have been to CAMHS and three-quarters have sought some professional help

3. Comorbidity • About one-third of cases have another mental disorder • About two-thirds have either a physical of developmental disorder

4. Costs of Antisocial Behaviour From Scott, 2001

5. Conduct Disorder is Associated with Many Psychiatric Outcomes From Kim-Cohen et al, Arch. Gen Psychiatry., 2003

6. Treatment Effects • Community parenting programs of preschoolers • non-significant effect favouring intervention • Research/academic programs for preschool to primary school • 0.5-1.0 SD treatment effect • Multisystemic therapy • 0.5 SD treatment effect

7. Heritabilities for Conduct Disorder

8. What do we know about precursors of antisocial behaviour?

9. Cognitive Risk Factors for Antisocial Behaviour • Low IQ • Low verbal skills • Deficits in executive functioning, including attentional problems • Poor academic attainments • ? Cause or effect

10. Parental Risk Factors for Antisocial Behaviour • Marital discord • Paternal criminality • Maternal depression • Poor parental supervision • Harsh and inconsistent discipline Are family factors environmental or genetic? Are they causal or responsive?

11. Maternal Depression after Birth Relates to Conduct Problems No depression Before & after birth Before birth After birth From Kim-Cohen et al, Arch Gen Psychiat 2005

12. Amount of Maternal Depression and Conduct Problems Number of depressive episodes 0 1 2 3

13. Contribution of Maternal Disorder to Conduct Problems Without ASPD With ASPD

14. Reciprocal influences of parental discipline and antisocial behaviour: Evocative gene-environment correlation Adoptive parents’ disciplinary practices Adoptive parents’ Marital warmth Adoptees’ Antisocial behaviour Biological parents’ Psychiatricdisorder

15. Genetic Effects of Parental Discipline Style From Lau et al, 2006, JCPP

16. Monoamine Oxidate A • X linked • Genetic mutation lading to reduced MAO A activity associated with mild mental retardation and impulsive behaviour • No evidence for direct role of MAO A in antisocial behaviour

17. Effect of Monoamine Oxidase A on Brain Low MAO A activity associated with: • Reduced volume of amygdala, cingulate gyrus insula and hypothalamus • Increased amygdala activation to emotional arousal and emotional memory (latter in males only) • Decreased anterior cingulate activation to inhibition in males only From Meter-Linden berg et al (2006) PNAS

18. Interaction between monoamine oxidase A gene and maltreatment from Caspi et al (2002)

19. Social Risk Factors for Antisocial Behaviour • Family poverty • Minority ethnic status

20. Familial Transmission of Antisocial Behaviour:Passive Gene-Environment Correlation

21. Effect of Neighbourhood on Heritability of Antisocial Behaviour From Tuvblad et al, 2006 JCPP

22. Neighbourhood Influences on Antisocial Behaviour • Urban environment • High crime neighbourhood • Neighbourhood with high drug availability • Neighbourhood social cohesion • Exposure to violence • Delinquent peer group Access to antisocial activities may increase antisocial behaviour

23. School Effects on Conduct Problems • School variation in delinquency, disruptiveness and absenteeism, having accounted for intake characteristics • ‘better’ behaviour associated with school characteristics of: • Clear leadership • Good classroom management • Academia emphasis • Consistent sanctions for misbehaviour

24. Heritability of ADHD Twin Studies of Parental Reports Eaves et al Price et al Gjone Goodman Thaparetal Gjone Levy et al

25. Shared genetic effects between ADHD and conduct disorder ADHD Conductdisorder Phenotypic correlation 0.3

26. Shared genetic effects between ADHD and conduct disorder Genes Conduct Disorder ADHD Environment Environment

27. Symptoms of ADHD predisposing to conduct disorder Genes Genes Conduct Disorder ADHD Environment Environment

28. Association of DRD4 with ADHD Susceptibility genes are neither necessary nor sufficient to cause disease from LaHoste et al (1996)

29. Case-control Studies of ADHD & DRD4 Thapar (1999) Swanson (1998) Rowe (1998) La Hoste (1996) Kennedy (1999) Holmes (1999) Comings (1999) Castellanos (1998) Asherson (1998) 0 1 2 3 4 5 6 7 8 Odds Ratio N cases = 1266; N controls = 3068, p=0.00000008. Combined OR = 1.9 (1.5 – 2.2). Genome-wide significance level (1 per genome scan for association) Faraone et al. 2000

30. Molecular Genetics of ADHDGenetic Associations replicated not replicated DRD4 yes yes DAT1 yes yes DßHydroxylase yes yes Dopa decarboxylase no no serotonin transporter yes no serotonin 2A receptor no no COMT no yes MAOA yes yes

31. Implications for Early DetectionShould genetic tests be used to guide us in determining who is at risk • How sensitive and specific are genetic tests in determining who will have disorder? • Will early detection alter the prognosis or treatment for disorder? • Are genetic studies the most efficient in identifying at risk populations?

32. Genetic Influences on Antisocial Behaviour Increase with Age

33. Long-term effect of hyperactivity on antisocial behaviour

34. Unreliable Untruthful Lack guilt Misbehave for no purpose Do not learn from punishment Poor judgment Don’t plan Insincere Self-centered No close relationships No deep emotions Lack personal insight Unresponsive to kindness or praise Genetic Influences on Psychopathic Behaviour Minnesota Temperament Inventory Antisocial scale Detachment scale From Taylor et al (2003)

35. Genetic Influences on Psychopathic Behaviour Minnesota Temperament Inventory

36. Does not show feelings or emotions helpful if someone is hurt, upset or feeling ill feels bad or guilt when done something wrong considerate of others’ feelings kind to younger children concerned about how well s/he is doing in school Often has temper tantrums or hot tempers generally obedient, usually does what adults request often lies or cheats steals from home school or elsewhere Callous/unemotional and antisocial behaviour in 7 year olds Callous/unemotional Antisocial Viding et al 2005

37. Childhood callous/unemotional traits and antisocial behaviour Viding et al, 2005

38. Callous Unemotional Children Make More Errors Recognizing Sad/Fearful Faces From Blair et al, 2000

39. Cognitive Dysfunction in Psychopathy • Failure to make stimulus-reinforcement associations particularly in relation to fearful or distressed stimuli • Disruption in ability to alter stimulus-response associations

40. Similar Communication Profiles in Children with Conduct Disorder and ASD

41. Deficits in Emotional Recognition in Hard to Mange Preschoolers From Hughes et al JCPP, 1998

42. Insensitivity of CU Children to Parenting Programs From Dadds & Hawes, in press

43. Origins of Phenotypic Continuity Genes time 1 Genes time 2 Genes time 3 Behaviour Time 1 Behaviour Time 2 Behaviour Time 3 Environment time 1`` Environment time 2 Environment time 3

44. Implications for Research Directions • Studies of antisocial behaviour need to begin early in life • Risk factor research must start with adequate description of the child on a variety of dimensions • Integration of measurement of risk factors from many perspectives is necessary