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Gene and environment interplay Future directions
for psychological research.
Jim Stevenson Developmental Brain-Behaviour
Unit School of Psychology University of
Southampton
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Developmental Brain-Behaviour Unit School of
Psychology
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Rutter, M (2005) Genes and behaviour
Nature-nurture interplay explained. Oxford
Blackwell
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Published in 2003 by American Psychological
Association
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Outline of session
Studies of genetic and environmental risk
Unknown E and unknown G Unknown E and
identified G Identified E and unknown
G Identified E and identified G
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Outline of session
Concepts in gene-environment interplay Strategie
s for investigating GxE Example of COMT and
antisocial behaviour in children with ADHD -
Thapar et al. (2005) if I have time!
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• Studies of genetic and environmental risk

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Unknown E. and unknown G. Becker-Blease et al
(2004) JCPP, 45, 522-532
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Unknown E. and unknown G. Becker-Blease et al
(2004) JCPP, 45, 522-532
Dissociative experiences include amnesia,
identity disturbance, age regression, difficulty
with concentration, and trance states. Stable
individual differences in dissociative behaviors
may represent a dissociative tendency trait that
varies in the population independent of the
influence of trauma.
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Unknown E. and unknown G. Neiss et al (2005) J
Personality and Social Psychology, 89, 593-606
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The executive self refers to the agentic aspect
of the self-system, the part involved actively in
monitoring itself, choosing how to behave, and
enacting chosen responses. The executive self
encompasses several phenomena, including control
beliefs, control strategies, and self-regulation
Self-esteem is the overall evaluation of the self
reflecting how much individuals accept and like
themselves.
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Covariation among the 3 phenotypes reflected
largely common genetic influences, although
unique genetic effects explained variability in
both executive self and negative affectivity.
Executive self was influenced by shared
environmental influences unique from those
affecting self-esteem and negative affectivity.
Nonshared environmental influences accounted for
the majority of variance in each construct and
were primarily unique to each. The unique
genetic and nonshared environmental influences
support the proposition that the executive self,
self-esteem, and negative affectivity capture
distinct and important differences between
people.
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Unknown E. and Identified G. Cope et al. (2005)
Am J of Human Genetics 76,581-591
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Progress towards an understanding of the genetics
of reading disability
Exciting, challenging and possibly worrying
developments. To date after nearly 10 years of
work the first gene has been identified that
contributes to reading disability in a
significant proportion of the the general
population. This first gene is a) of small
effect, and b) subsequent genes are going to be
of smaller effect and harder to find. Future
progress will be slow and the impact on practice
not immediately dramatic.
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More progress has been made with reading than
with genetic studies on any other higher order
cognitive ability. Reading is probably more
highly heritable than other cognitive
abilities. For this reason progress in other
aspects of individual difference in cognition is
likely to be even slower
e.g. specific mathematical ability
(dyscalculia), working memory
and
executive functions Allelic variation in any one
gene are unlikely to have specific associations
with one aspect of cognition. Genetic effects are
likely to be mediated via complex gene-gene and
gene-environment interactions
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Identified E. and unknown G. Eley Stevenson
(2000) J Ab Child Psychol 28,383-394
Depressed proband had significantly more LOSS
events than controls - but not significantly more
THREAT events Anxious probands had significantly
more THREAT events than controls - but not
significantly more LOSS events
Anxiety
Genetic risk
threat
Depression
loss
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Breakthroughs of the year
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Identified E. and Identified G. Caspi et al.
(2003) Science 301,386-389
5HTT serotonin transporter
s genotype
l genotype
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Identified E. and Identified G. Caspi et al.
(2002) Science 297,851-854
Results
Having the high MAOA version of the gene promotes
resilience when experiencing maltreatment
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Identified E. and Identified G. Pre-publication
shown in confidence
Mean 95 CI
Paired t-test G present t 0.27, df 23, ns G
absent t 2.59, df 44, lt.014 Effect size G
present 0.048 G absent 0.236 using Total
Placebo SD
G present G absent
ADRA2A
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Summary of studies of genetic and environmental
risk

• Unknown E. and Unknown G. (e.g. self esteem)
• information about population not individuals
• Unknown E. and Identified G. (e.g. reading)
• little immediate clinical relevance
• Identified E. and unknown G. (e,g, anxiety and
  depression)
• implications for understanding case histories
• Identified E. and Identified G. (e,g, additives
  and ADRA2A)
• direct relevance for identifying risk and
  possibly for guiding intervention

The greater the knowledge of E. the more valuable
the understanding of G. becomes
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Gene- environment interplay
Rutter, M., Moffitt, T.E. Caspi, A. (2006).
Gene-environment interplay and psychopathology
multiple varieties but real effects. Journal of
Child Psychology and Psychiatry (electronic
pre-print).
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Rutter et al. (2006)
The main messages that derive from this review
of geneenvironment interplay in the origins of
psychopathology are
1. there are several quite different forms of
interplay, each of which has rather different
implications
2. each, however, involves the basic point that
the effects of genes and the effects of
environments are not as separate as was once
supposed
3. the findings on epigenetic effects provide a
convincing demonstration that, through influences
on gene expression, environments can and, in
certain circumstances, do moderate the effects of
genes in crucially important ways
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Rutter et al. (2006)
4. variations in heritability according to
environmental circumstances can be considerable,
but focused, testable hypotheses and unambiguous
comparisons are needed. As a result, this
research approach has had little success so far
in casting light on causal mechanisms
5. there are several different types of
geneenvironment correlations (rGE) that play a
substantial role in influencing environmental
risk exposure but their impact is through the
effects of parent and child behaviours in shaping
and selecting environments
6. geneenvironment interactions (GxE) have been
shown for several disorders and are likely to
prove to be important in a broader range of
multifactorial conditions
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Rutter et al. (2006)
7. the study and elucidation of the mechanisms
involved in the different forms of
geneenvironment interplay should cast important
light on basic causal mechanisms for
psychopathology
8. an understanding of the complexities involved
in geneenvironment interplay may also help in
avoiding misleading types of biological
reductionism and stigma, whilst at the same time
emphasising the importance of genes in all risk
and protection pathways.
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http//www.nuffieldbioethics.org/filelibrary/pdf/n
uffieldgeneticsrep.pdf
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Strategies for investigating G E interplay
Moffitt, T. E., Caspi, A., Rutter, M. (2005).
Strategy for investigating interactions between
measured genes and measured environments.
Archives Of General Psychiatry, 62, 473-481.
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Cost of genotyping
Using KBioscience based on 544 genotypes 136
children each with 4 SNPs 1-94 per SNP all lab
costs after receiving cheek cell swabs
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Thapar et al (2005)
Background
Early onset antisocial behaviour (AB) plus ADHD
is a severe condition with poor prognosis. Range
of genetic and early prenatal environmental
influences though important. Prefrontal cortex
(PFC) implicated. Catecol-methyl transferase
(COMT) has a role in PFC val short isoform has
higher activity and therefore lowers dopamine in
PFC. Birthweight is an index of quality of
maternally determined prenatal environment.
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Thapar et al (2005)
Methods
240 clinic children (213 boys 27 girls). All
had DSM-IV diagnosis of ADHD 5 to 14
years. Exclusions IQlt70, autism, Tourette
syndrome, neurological conditions. CAPA used to
determine DSM-IV conduct disorder and ADHD. CD
symptom score used as dependent variable. Mothers
report on birthweight
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Thapar et al (2005)
Results
Genotype Frequency met/met 25 met/val 54 val/
val 21
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Thapar et al (2005)
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Thapar et al (2005)
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Thapar et al (2005)
Results
Regression results hold when maternal smoking in
pregnancy is controlled Replicated with logistic
regression using CD/not CD as dependent variable
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Thapar et al (2005)
Conclusions
Confirmed prediction of higher CD symptoms with
val/val genotyope. In addition val/val genotype
increased susceptibility to effects of low
birthweight on CD symptoms. No evidence that PFC
neuropsychological abilities mediate COMT CD
association perhaps bias from ADHD in
comparison group. The GxE interaction may be
valuable in identifying individuals at risk of
long term difficulties arising from adverse
prenatal events.
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For further details please email jsteven_at_soton.ac
.uk
Jim Stevenson Developmental Brain-Behaviour
Unit School of Psychology University of
Southampton
D
B
B U
Developmental Brain-Behaviour Unit School of
Psychology