Transcript Slide 1

Nature-Nurture Interplay in
Aggression and Antisocial
Behaviour
Emily Simonoff
Institute 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
£1508
Conduct
problems
£7524
Conduct
disorder
£12478
Foster/residential care
Health
£1320
£3412
£7647
£247
£1237
£2178
Crime
£2541
£8604
£44821
Total
£7423
£24324
£70179
Education
From Scott, 2001
Conduct Disorder is Associated
with Many Psychiatric Outcomes
odds ratio
Presence of Conduct Disorder by Age 15
4
3.5
3
2.5
2
1.5
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From Kim-Cohen et al, Arch. Gen Psychiatry., 2003
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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
0.8
0.6
0.4
0.2
0
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What do we know about precursors of
antisocial behaviour?
School
Cognitive
Behavioural &
Personality-Individual
Family
Neighbourhood
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
0.4
Conduct z scores
0.3
0.2
0.1
parent
teacher
0
-0.1
-0.2
-0.3
No
depression
Before birth
After birth
From Kim-Cohen et al, Arch Gen Psychiat 2005
Before & after
birth
Amount of Maternal Depression
and Conduct Problems
0.5
Conduct z score
0.4
0.3
0.2
parent
teacher
0.1
0
-0.1
-0.2
-0.3
Number of depressive episodes
0
1
2
3
Contribution of Maternal Disorder
to Conduct Problems
0.2
z conduct scores
0.15
0.1
0.05
not depressed
depressed
0
-0.05
-0.1
-0.15
-0.2
Without ASPD
With ASPD
Reciprocal influences of parental
discipline and antisocial behaviour:
Evocative gene-environment correlation
Adoptive parents’
Marital warmth
Biological parents’
Psychiatric disorder
Adoptive parents’
disciplinary practices
Adoptees’
Antisocial
behaviour
Genetic Effects of Parental
Discipline Style
1
0.8
0.6
0.4
0.2
0
punitive discipline
additive genetic
constructive discipline
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
% showing conduct disorder
100
80
60
40
20
0
high MAOA
no maltreatment
low MAOA
some maltreatment
severe maltreatment
from Caspi et al (2002)
Social Risk Factors for
Antisocial Behaviour
• Family poverty
• Minority ethnic status
Familial Transmission of Antisocial
Behaviour:
Passive Gene-Environment Correlation
genes
genes
.5
.21
CD
father
.5
(fixed)
CD
mother
.04
family
dysfunction
.19
genes
genes
E
E
.72
.5
CD
twin1
C
.45
CD
twin2
from Meyer at al (2000)
Effect of Neighbourhood on
Heritability of Antisocial Behaviour
1.00
0.80
0.60
0.40
0.20
0.00
advantaged
additive genetic
disadvantaged
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
1.0
0.8
0.6
0.4
0.2
0.0
Eaves et al
Thaparetal
Gjone
Gjone
Price et al
Goodman
Levy 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
ADHD
Environment
Conduct
Disorder
Environment
Symptoms of ADHD predisposing
to conduct disorder
Genes
Genes
ADHD
Conduct
Disorder
Environment
Environment
Association of DRD4 with ADHD
% allelic variation
with ADHD
without ADHD
<7 repeats
7-8 repeats
71
88
29
12
Susceptibility genes are neither necessary nor sufficient
to cause disease
from LaHoste et al (1996)
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
Molecular Genetics of ADHD
Genetic Associations
replicated
DRD4
DAT1
DßHydroxylase
Dopa decarboxylase
serotonin transporter
serotonin 2A receptor
COMT
no
MAOA
not replicated
yes
yes
yes
no
yes
no
yes
yes
yes
no
no
no
yes
yes
yes
Implications for Early Detection
Should 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
2.2
hyperactivity
7.7
conduct 5.0
disorder
antisocial 29.6
personality
age 21-30
antisocial
personality
age 31+
20.3
2.7
delinquent
peer group
Simonoff et al (2004)
Genetic Influences on Psychopathic
Behaviour
Minnesota Temperament Inventory
Antisocial scale
• Unreliable
• Untruthful
• Lack guilt
• Misbehave for no purpose
• Do not learn from
punishment
• Poor judgment
• Don’t plan
Detachment scale
• Insincere
• Self-centered
• No close relationships
• No deep emotions
• Lack personal insight
• Unresponsive to kindness
or praise
From Taylor et al (2003)
Genetic Influences on Psychopathic
Behaviour
Minnesota Temperament Inventory
Variance component
1.2
1
0.8
0.6
0.4
0.2
0
Antisocial scale
aditive genetics
Detachment Scale
unique environment
Callous/unemotional and antisocial
behaviour in 7 year olds
Callous/unemotional
• 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
Antisocial
• Often has temper
tantrums or hot tempers
• generally obedient,
usually does what adults
request
• often lies or cheats
• steals from home school
or elsewhere
Viding et al 2005
Childhood callous/unemotional
traits and antisocial behaviour
variance component
1
0.8
0.6
0.4
0.2
0
antisocial
caullous unemotional
behaaviour/high C/U
traits
genes
common environment
antisocial behaviour
nl C?U
unique envionment
Viding et al, 2005
Callous Unemotional Children Make More
Errors Recognizing Sad/Fearful Faces
1.6
errors
1.2
0.8
0.4
0
Sad
Fear
Happy
CU
From Blair et al, 2000
Surprise
Comparison
Disgust
Anger
Cognitive Dysfunction in Psychopathy
• Failure to make stimulus-reinforcement
associations particularly in relation to
fearful or distressed stimuli
• Disruption in ability to alter stimulusresponse associations
Similar Communication Profiles in
Children with Conduct Disorder and ASD
Children's Communication Checklist % Clinical
Range
100
80
60
40
20
0
Use of Context
Conduct
Rapport
ASD
Social
Relationships
Autism
Interests
Typically developing
Deficits in Emotional Recognition
in Hard to Mange Preschoolers
main effects of group, story type & emotion type
mean score
4
3.5
happy
sad
angry
scared
3
2.5
2
H2M
control
unambiguous stories
From Hughes et al JCPP, 1998
H2M
control
ambiguous sotries
Insensitivity of CU Children to
Parenting Programs
oppositional defiant symptoms
5
score
4
3
low CU
High CU
2
1
0
pre-treatment
post-treatment
follow-up
From Dadds & Hawes, in press
Origins of Phenotypic Continuity
Genes time 1
Behaviour
Time 1
Environment
time 1``
Genes time 2
Genes time 3
Behaviour
Time 2
Behaviour
Time 3
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