Nature-Nurture Interplay in Aggression and Antisocial

Behaviour

Emily SimonoffInstitute of Psychiatry

London

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

Comorbidity

• About one-third of cases have another mental disorder

• About two-thirds have either a physical of developmental disorder

Costs of Antisocial Behaviour

No problems

Conduct problems

Conduct disorder

Education £1508 £7524 £12478

Foster/resi-dential care

£1320 £3412 £7647

Health £247 £1237 £2178

Crime £2541 £8604 £44821

Total £7423 £24324 £70179

From Scott, 2001From Scott, 2001

Conduct Disorder is Associated with Many Psychiatric Outcomes

Presence of Conduct Disorder by Age 15

11.5

22.5

33.5

4

anxiety

depression

maniaeating

schizophrenia

substance

APSD

odds

ratio

From Kim-Cohen et al, Arch. Gen Psychiatry., 2003

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

Heritabilities for Conduct Disorder

0

0.2

0.4

0.6

0.8

Eaves et alEaves et alSlutske et alGjone & Stevenson

Gjone & Stevenson

Thapar & McGuffin

Lyons et alEdelbrock et alRowe

Zahn-Waxler

Gelhorn

What do we know about precursors of antisocial behaviour?

Cognitive

Family

School

Neighbourhood

Behavioural &Personality--Individual

Cognitive Risk Factors for Antisocial Behaviour

• Low IQ• Low verbal skills• Deficits in executive functioning, including

attentional problems• Poor academic attainments

– ? Cause or effect

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?

Maternal Depression after Birth Relates to Conduct Problems

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

Con

duct

z s

core

s

parentteacher

No depression Before birth After birth

Before & after birth

From Kim-Cohen et al, Arch Gen Psychiat 2005

Amount of Maternal Depression and Conduct Problems

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

Con

duct

z s

core

parent teacher

0 1 2 3

Number of depressive episodes

Contribution of Maternal Disorder to Conduct Problems

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

z co

nduc

t sco

res

not depresseddepressed

Without ASPD With ASPD

Reciprocal influences of parental discipline and antisocial behaviour:

Evocative gene-environment correlation

Adoptive parents’ Marital warmth

Adoptive parents’disciplinary practices

Biological parents’Psychiatric disorder

Adoptees’Antisocial behaviour

Genetic Effects of Parental Discipline Style

0

0.2

0.4

0.6

0.8

1

punitive discipline constructive discipline

additive genetic common environmental unique environmental

From Lau et al, 2006, JCPP

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

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

Interaction between monoamine oxidase A gene and maltreatment

from Caspi et al (2002)

% showing conduct disorder

0

20

40

60

80

100

high MAOA low MAOA

no maltreatment some maltreatment severe maltreatment

Social Risk Factors for Antisocial Behaviour

• Family poverty• Minority ethnic status

Familial Transmission of Antisocial Behaviour:

Passive Gene-Environment Correlation

genes genes

genesgenes

CDfather

CDmother

familydysfunction

CDtwin1

CDtwin2

E E

.5

.21

.04

.5(fixed)

.5

.19

C

.45

.72

from Meyer at al (2000)

Effect of Neighbourhood on Heritability of Antisocial Behaviour

0.00

0.20

0.40

0.60

0.80

1.00

advantaged disadvantaged

additive genetic shared environemntal unique environmental

From Tuvblad et al, 2006 JCPP

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

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

Heritability of ADHD

Twin Studies of Parental Reports

0.0

0.2

0.4

0.6

0.8

1.0

Eaves et alThaparetal

GjoneGjone

GoodmanLevy et al

Price et al

Shared genetic effects between ADHD and conduct disorder

ADHD Conduct disorder

Phenotypic correlation 0.3

Shared genetic effects between ADHD and conduct disorder

Genes

ADHDConduct Disorder

Environment Environment

Symptoms of ADHD predisposing to conduct disorder

Genes

ADHD

Environment

Genes

Conduct Disorder

Environment

Association of DRD4 with ADHD

% allelic variation

<7 repeats 7-8 repeats

with ADHD 71 29without ADHD 88 12

Susceptibility genes are neither necessary nor sufficient to cause disease

from LaHoste et al (1996)

Asherson (1998)

Castellanos (1998)

Comings (1999)

Holmes (1999)

Kennedy (1999)

La Hoste (1996)

Rowe (1998)

Swanson (1998)

Thapar (1999)

0 1 2 3 4 5 6 7 8Odds 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)

Case-control Studies of ADHD & DRD4

Faraone et al. 2000

Molecular Genetics of ADHDGenetic Associations

replicated not replicated

DRD4 yes yesDAT1 yes yesDßHydroxylase yes yesDopa decarboxylase no noserotonin transporter yes noserotonin 2A receptor no noCOMT no yesMAOA yes yes

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?

Genetic Influences on Antisocial Behaviour Increase with Age

Childhood conduct disorder Adult antisocial personality

gene common environment unique environment

Long-term effect of hyperactivity on antisocial behaviour

hyperactivity conductdisorder

antisocialpersonalityage 21-30

antisocialpersonalityage 31+

7.7 5.0 29.6

2.2

delinquentpeer group

2.7

20.3

Simonoff et al (2004)

Genetic Influences on Psychopathic Behaviour

• 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

Minnesota Temperament Inventory

From Taylor et al (2003)

Antisocial scale Detachment scale

Genetic Influences on Psychopathic Behaviour

Minnesota Temperament Inventory

0

0.2

0.4

0.6

0.8

1

1.2

Antisocial scale Detachment Scale

Varia

nce

com

pone

nt

aditive genetics unique environment

Callous/unemotional and antisocial behaviour in 7 year olds

• 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 Antisocial

Viding et al 2005

Childhood callous/unemotional traits and antisocial behaviour

0

0.2

0.4

0.6

0.8

1

caullous unemotionaltraits

antisocialbehaaviour/high C/U

antisocial behaviournl C?U

varia

nce

com

pone

nt

genes common environment unique envionment

Viding et al, 2005

Callous Unemotional Children Make More Errors Recognizing Sad/Fearful Faces

0

0.4

0.8

1.2

1.6

Sad Fear Happy Surprise Disgust Anger

erro

rs

CU Comparison

From Blair et al, 2000

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

Similar Communication Profiles in Children with Conduct Disorder and ASD

Children's Communication Checklist % Clinical Range

020406080

100

Use of Context Rapport SocialRelationships

Interests

Conduct ASD Autism Typically developing

Deficits in Emotional Recognition in Hard to Mange Preschoolers

main effects of group, story type & emotion type

2

2.5

3

3.5

4

H2M control H2M control

unambiguous stories ambiguous sotries

mea

n sc

ore happy

sadangryscared

From Hughes et al JCPP, 1998

Insensitivity of CU Children to Parenting Programs

oppositional defiant symptoms

0

1

2

3

4

5

pre-treatment post-treatment follow-up

scor

e low CUHigh CU

From Dadds & Hawes, in press

Origins of Phenotypic Continuity

Behaviour Time 1

Behaviour Time 2

Behaviour Time 3

Genes time 1 Genes time 2 Genes time 3

Environment time 1``

Environment time 2

Environment time 3

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