Genetic Foundations
of Mind & Behavior
Honors Psychology
Two Main Questions
•
•
The Classic Nature-Nurture Question:
Are there biological reasons for why people are so
different from one another? (Behavioral Genetics)
The New Nature-Nurture Question:
How is the nervous system built? (Developmental
Neuroscience)
•
•
Two Main Questions
•
The Classic Nature-Nurture Question:
Are there biological reasons for why people are so
different from one another? (Behavioral Genetics)
NOT “What matters more--the genes or the
environment?”
•
•
What makes a rectangle big?
height or length?
6”
9”
What makes a rectangle big?
Area = height X length!
6”
9”
What makes us X?
nature or nurture?
genes or environment?
Genetic and Environmental Forces
•
Hereditary and environmental interactions are
best illustrated by this model:
Genetic and Environmental Forces
•
Hereditary and environmental interactions are
best illustrated by this model:
•
•
•
Children get all of their genes from their parents.
A gene is a segment of DNA that is the code for the
production of one particular protein
Genes affect development
by specifying a protein template
by regulating other genes
•
•
•
•
Children get all of their genes from their parents.
Each parent contributes 50% of the child’s genes
•
•
Because
chromosomes come in
pairs (one from each
parent), so do genes
Some pairs of genes
are identical
(homozygous) and
some are not
(heterozygous)
•
The difference between homozygous and
heterozygous gene pairs (alleles) has implications
for how the child’s genotype affects his/her
phenotype
2
GENOTYPE/Child → PHENOTYPE/Child
2
GENOTYPE/Child → PHENOTYPE/Child
•
Two ways children’s genes affect their behavior
One gene can control behavior (Mendelian inheritance)
Many genes can control behavior (Polygenic inheritance)
•
•
2
GENOTYPE/Child → PHENOTYPE/Child
•
A third of genes have two or more different forms,
known as alleles.
Some physical traits, such as straight hair, require
matching “recessive” alleles, one from each parent, for
expression.
Others, such as curly hair, require only the inheritance of
one “dominant” allele, which will override a “recessive”
allele from the other parent.
When traits are controlled by a single allele, a
Mendelian distribution will be observed
•
•
•
Mendelian distribution:
Mendel’s Peas
Mendelian distribution:
Hair Color
Mendelian distribution:
Wizarding
Mendelian Psychological Traits
•
•
Like the skin of peas, hair color,
and wizarding, some
psychological traits also appear
to be controlled by a single gene
Scott & Fuller (1965)
found that all bansenjis were afraid
of a novel person, whereas the
cocker spaniels were seldom
afraid.
Was there a genetic link?
•
•
Mendelian Distribution:
Fear Responses
•
•
•
First, they crossbred pure
cockers and pure basenjis.
Some hybrids were raised
by cockers; some by
basenjis.
All hybrids were fearful, like
purebred basenjis
They hypothesized that
fearfulness was controlled
by a singe dominant gene
Mendelian Distribution:
Fear Responses
•
•
To test their hypothesis,
they crossbred the
hybrids.
They found the same
pattern Mendel found
with the peas.
FF
Ff
Mendelian Distribution:
Fear Responses
•
Finally, they
backcrossed the original
hybrids with purebred
cockers.
Half were afraid (like the
basenji), and half were
not (like the cockers), just
as one would predict if a
single fear-controlling
gene were dominant.
•
Mendelian Distribution: PKU & SLI
•
•
PKU—Phenylketonuria: total
language loss and mental
retardation (prevented by
monitoring the child’s diet)
SLI—Specific Language
Impairment has been
linked to the FOXp2 gene
Polygenic Distribution
•
Most traits and behaviors of psychological interest
involve contributions by several genes, such as
infant temperament
shyness
aggression
risk-taking behavior
empathy
TV viewing
•
•
•
•
•
•
Polygenic Distribution
•
When many individuals are tested for a polygenic
characteristics, the results follow a normal
distribution.
What is
this kind of
figure
called?
Population Genetics
•
Population genetics
attempts to find a role for genes by looking at differences
between people and linking it to (genetic) family history
ask how much variation in the behavior of a group is a
function of genetic differences (”heritability”, h2) versus
environmental differences
If h2 = 1, all of the differences stem from genetic
differences
If h2 = 0, none of the differences stem from genetic
differences
If h2 = .5, half of the differences stem from genetic
•
•
•
•
•
Variation in Area
World A
World B
Variation due to heights
Variation due to lengths
How much of the variation in area is a function of
height versus width?
Variation in Behavior
World A
World B
Variation due to heights
Variation due to lengths
How much of the variation in behavior is a function of
genetic differences versus environmental differences?
Heritability
•
Familiality versus Heritability
Traits are familial if members of the same family share
them, for whatever reason—whether shared genotypes
or shared environments
Traits are heritable only if the similarity arises from
shared genotypes.
In experimental organisms, such as fruit flies, it is
possible to control the environment and thereby
distinguish effects of genetic similarity vs. effects of
environmental similarity.
•
•
•
Experiment to Establish Heritability
Tryon’s Study of Maze Learning
•
Tryon (1942)
This chart depicts the progress
Tryon made in selectively
breeding rats for their ability to
get through mazes after only a
few errors.
The critical step Tryon made
was to cross-foster the rats
(bright rats raised by dull rats,
dull rats raised by bright
ones). Regardless, offspring
scores resembled those of
their parents.
•
•
Estimating H2
•
•
In humans, less control over environmental
similarity is possible.
Two common strategies:
To estimate environmentality—the proportion of
variance due to environmental variation, compare
identical twins raised apart (some environmental
similarity) to identical twins raised together (more
environmental similarity)
To estimate heritability—the proportion of variance due
to genetic variation, compare identical twins raised
together (some environmental similarity) to fraternal
twins raised together (same amount of environmental
similarity)
•
•
Family Studies of IQ
Relationship
Correlation
MZ, reared together
0.86
DZ, reared together
0.60
MZ, reared apart
0.72
unrelated, reared together
0.00
h2= (MZ - DZ) x 2
= (.86-.60) x 2
= .52
e2= (MZrt - MZra)
= .86-.72
= .14
3
ENVIRONMENT/Child → PHENOTYPE/Child
3
ENVIRONMENT/Child → PHENOTYPE/Child
• Genotypes are expressed differently in
different environments.
• The “norm of reaction” is the range of all
possible phenotypes in relation to all
possible environments.
Family Studies of IQ
Relationship
Correlation
!
T
0.86
N
A
T
S
N
O
DZ, reared together A C
0.60
T
O
N
S
2
I
MZ, reared apart
0.72
H
MZ, reared together
unrelated, reared together
h2= (MZ - DZ) x 2
= (.86-.60) x 2
= .52
0.00
e2= (MZrt - MZra)
= .86-.72
= .14
Norm of reaction: Example #1
•
For the sake of argument, assume that depression/
happiness is entirely the result of genetics
Who is most likely to be depressed?
A
Mr. A’s identical twin has a
history of depression
B
Mr. B’s identical twin has no
history of depression
C
Mr. C’s fraternal twin has a
history of depression
D
Mr. D’s fraternal twin has no
history of depression
Norm of reaction: Example #1
A
C
D
B
Kendler et al. (1995) Am J Psychiatry, 152, 833-842
tivity (25) that investigated two tasks with right
hemisphere dominance demonstrated top-down
effects that were specific for the right hemisphere, i.e., from the right middle frontal gyrus
(area 46) on right extrastriate areas. It is thus
likely that our findings generalize to other lateralized tasks. Although we cannot exclude lateralization contingent on stimulus type in some
situations, our results are consistent with previous findings from split-brain patient studies (7)
and positron emission tomography (11) showing
hemispheric specialization based on task demands. Research on hemispheric specialization
should move beyond analyses of asymmetric
regional activations and focus more strongly on
functional interactions within and between
hemispheres.
19. A. W. MacDonald, J. D. Cohen, V. A. Stenger, C. S.
Carter, Science 288, 1835 (2000).
20. B. J. Casey et al., Proc. Natl. Acad. Sci. U.S.A. 97,
8728 (2000).
21. C. S. Carter et al., Proc. Natl. Acad. Sci. U.S.A. 97,
1944 (2000).
National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, and the
National Cancer Institute. We thank our volunteers,
K. Amunts for helpful anatomical discussions, and the
radiographers at the Research Center Jülich for technical assistance.
Supporting Online Material
www.sciencemag.org/cgi/content/full/301/5631/384/DC1
Materials and Methods
References
Downloaded from www.sciencemag.org on January 12, 2009
ed) during visuospatial decisions. Note the specificity of this result: Even when the threshold was
reduced to P # 0.05, uncorrected, no other significant clusters were found throughout the brain.
(B) This schema summarizes the negative findings for right ACC: As indicated by the gray dashed
lines, right ACC shows no context-dependent contributions to any left-hemispheric area during
visuospatial decisions and none to any left- or right-hemispheric area at all during letter decisions.
Norm of reaction: Example #1
Influence of Life Stress on
Depression: Moderation by a
Polymorphism in the 5-HTT Gene
REPORTS
References and Notes
1. J. L. Bradshaw, N. C. Nettleton, Behav. Brain Sci. 4, 51
(1981).
2. J. B. Hellige, Annu. Rev. Psychol. 41, 55 (1990).
3. J. C. Marshall, Behav. Brain Sci. 4, 72 (1981).
4. K. Hugdahl, R. J. Davidson, The Asymmetrical Brain
(MIT Press, Cambridge, MA, 2003).
5. J. Sergent, Psychol. Bull. 93, 481 (1983).
6. C. Chiarello, J. Senehi, M. Soulier, Neuropsychologia 4,
521 (1986).
7. P. M. Corballis, M. G. Funnell, M. S. Gazzaniga, NeuroReport 10, 2183 (1999).
8. C. J. Price, R. J. S. Wise, R. S. J. Frackowiak, Cereb.
Cortex 6, 62 (1996).
9. G. R. Fink et al., Nature 382, 626 (1996).
10. L. E. Nystrom et al., Neuroimage 11, 424 (2000).
11. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,
Cereb. Cortex 6, 39 (1996).
12. J. Levy, C. Trevarthen, J. Exp. Psychol. Hum. Percept.
Perform. 2, 299 (1976).
13. M. S. Gazzaniga, Brain 123, 1293 (2000).
14. M. I. Posner, S. E. Petersen, Annu. Rev. Neurosci. 13,
25 (1990).
15. T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
16. R. Desimone, J. Duncan, Annu. Rev. Neurosci. 18, 193
(1995).
17. Materials and methods are available as supporting
material on Science Online.
18. Using a 2 ! 2 ! 2 factorial design, with letter vs.
visuospatial decisions, left vs. right visual fields of
presentation, and left vs. right response hand as the
three experimental factors, the eight conditions occurred equally often and were varied systematically
as blocked conditions in a pseudorandom fashion.
386
23 April 2003; accepted 6 June 2003
Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2*
Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2
Joseph McClay,1 Jonathan Mill,1 Judy Martin,3
Antony Braithwaite,4 Richie Poulton3
In a prospective-longitudinal study of a representative birth cohort, we tested
why stressful experiences lead to depression in some people but not in others.
A functional polymorphism in the promoter region of the serotonin transporter
(5-HT T) gene was found to moderate the influence of stressful life events on
depression. Individuals with one or two copies of the short allele of the 5-HT T
promoter polymorphism exhibited more depressive symptoms, diagnosable
depression, and suicidality in relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual’s response
to environmental insults is moderated by his or her genetic makeup.
Depression is among the top five leading causes
of disability and disease burden throughout the
world (1). Across the life span, stressful life
events that involve threat, loss, humiliation, or
defeat influence the onset and course of depresMedical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College London, PO80 De Crespigny Park,
London, SE5 8AF, UK. 2Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3Dunedin School of Medicine, 4Department of Pathology,
University of Otago, Dunedin, New Zealand.
1
*To whom correspondence should be addressed. Email: t.moffitt@iop.kcl.ac.uk
sion (2–5). However, not all people who encounter a stressful life experience succumb to
its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup (6, 7). Behavioral genetics research supports this prediction, documenting
that the risk of depression after a stressful event
is elevated among people who are at high genetic risk and diminished among those at low
genetic risk (8). However, whether specific
genes exacerbate or buffer the effect of stressful
life events on depression is unknown. In this
study, a functional polymorphism in the pro-
18 JULY 2003 VOL 301 SCIENCE www.sciencemag.org
s = allele for
“short” serotonin
transporter
l = allele for
“long” serotonin
transporter
tivity (25) that investigated two tasks with right
hemisphere dominance demonstrated top-down
effects that were specific for the right hemisphere, i.e., from the right middle frontal gyrus
(area 46) on right extrastriate areas. It is thus
likely that our findings generalize to other lateralized tasks. Although we cannot exclude lateralization contingent on stimulus type in some
situations, our results are consistent with previous findings from split-brain patient studies (7)
and positron emission tomography (11) showing
hemispheric specialization based on task demands. Research on hemispheric specialization
should move beyond analyses of asymmetric
regional activations and focus more strongly on
functional interactions within and between
hemispheres.
19. A. W. MacDonald, J. D. Cohen, V. A. Stenger, C. S.
Carter, Science 288, 1835 (2000).
20. B. J. Casey et al., Proc. Natl. Acad. Sci. U.S.A. 97,
8728 (2000).
21. C. S. Carter et al., Proc. Natl. Acad. Sci. U.S.A. 97,
1944 (2000).
National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, and the
National Cancer Institute. We thank our volunteers,
K. Amunts for helpful anatomical discussions, and the
radiographers at the Research Center Jülich for technical assistance.
Supporting Online Material
www.sciencemag.org/cgi/content/full/301/5631/384/DC1
Materials and Methods
References
Downloaded from www.sciencemag.org on January 12, 2009
ed) during visuospatial decisions. Note the specificity of this result: Even when the threshold was
reduced to P # 0.05, uncorrected, no other significant clusters were found throughout the brain.
(B) This schema summarizes the negative findings for right ACC: As indicated by the gray dashed
lines, right ACC shows no context-dependent contributions to any left-hemispheric area during
visuospatial decisions and none to any left- or right-hemispheric area at all during letter decisions.
Norm of reaction: Example #1
Influence of Life Stress on
Depression: Moderation by a
Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2*
Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2
Joseph McClay,1 Jonathan Mill,1 Judy Martin,3
Antony Braithwaite,4 Richie Poulton3
References and Notes
1. J. L. Bradshaw, N. C. Nettleton, Behav. Brain Sci. 4, 51
(1981).
2. J. B. Hellige, Annu. Rev. Psychol. 41, 55 (1990).
3. J. C. Marshall, Behav. Brain Sci. 4, 72 (1981).
4. K. Hugdahl, R. J. Davidson, The Asymmetrical Brain
(MIT Press, Cambridge, MA, 2003).
5. J. Sergent, Psychol. Bull. 93, 481 (1983).
6. C. Chiarello, J. Senehi, M. Soulier, Neuropsychologia 4,
521 (1986).
7. P. M. Corballis, M. G. Funnell, M. S. Gazzaniga, NeuroReport 10, 2183 (1999).
8. C. J. Price, R. J. S. Wise, R. S. J. Frackowiak, Cereb.
Cortex 6, 62 (1996).
9. G. R. Fink et al., Nature 382, 626 (1996).
10. L. E. Nystrom et al., Neuroimage 11, 424 (2000).
11. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,
Cereb. Cortex 6, 39 (1996).
12. J. Levy, C. Trevarthen, J. Exp. Psychol. Hum. Percept.
Perform. 2, 299 (1976).
13. M. S. Gazzaniga, Brain 123, 1293 (2000).
14. M. I. Posner, S. E. Petersen, Annu. Rev. Neurosci. 13,
25 (1990).
15. T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
16. R. Desimone, J. Duncan, Annu. Rev. Neurosci. 18, 193
(1995).
17. Materials and methods are available as supporting
material on Science Online.
18. Using a 2 ! 2 ! 2 factorial design, with letter vs.
visuospatial decisions, left vs. right visual fields of
presentation, and left vs. right response hand as the
three experimental factors, the eight conditions occurred equally often and were varied systematically
as blocked conditions in a pseudorandom fashion.
386
23 April 2003; accepted 6 June 2003
In a prospective-longitudinal study of a representative birth cohort, we tested
why stressful experiences lead to depression in some people but not in others.
A functional polymorphism in the promoter region of the serotonin transporter
(5-HT T) gene was found to moderate the influence of stressful life events on
depression. Individuals with one or two copies of the short allele of the 5-HT T
promoter polymorphism exhibited more depressive symptoms, diagnosable
depression, and suicidality in relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual’s response
to environmental insults is moderated by his or her genetic makeup.
Depression is among the top five leading causes
of disability and disease burden throughout the
world (1). Across the life span, stressful life
events that involve threat, loss, humiliation, or
defeat influence the onset and course of depresMedical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College London, PO80 De Crespigny Park,
London, SE5 8AF, UK. 2Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3Dunedin School of Medicine, 4Department of Pathology,
University of Otago, Dunedin, New Zealand.
1
*To whom correspondence should be addressed. Email: t.moffitt@iop.kcl.ac.uk
sion (2–5). However, not all people who encounter a stressful life experience succumb to
its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup (6, 7). Behavioral genetics research supports this prediction, documenting
that the risk of depression after a stressful event
is elevated among people who are at high genetic risk and diminished among those at low
genetic risk (8). However, whether specific
genes exacerbate or buffer the effect of stressful
life events on depression is unknown. In this
study, a functional polymorphism in the pro-
18 JULY 2003 VOL 301 SCIENCE www.sciencemag.org
s = allele for
“short” serotonin
transporter
l = allele for
“long” serotonin
transporter
tivity (25) that investigated two tasks with right
hemisphere dominance demonstrated top-down
effects that were specific for the right hemisphere, i.e., from the right middle frontal gyrus
(area 46) on right extrastriate areas. It is thus
likely that our findings generalize to other lateralized tasks. Although we cannot exclude lateralization contingent on stimulus type in some
situations, our results are consistent with previous findings from split-brain patient studies (7)
and positron emission tomography (11) showing
hemispheric specialization based on task demands. Research on hemispheric specialization
should move beyond analyses of asymmetric
regional activations and focus more strongly on
functional interactions within and between
hemispheres.
19. A. W. MacDonald, J. D. Cohen, V. A. Stenger, C. S.
Carter, Science 288, 1835 (2000).
20. B. J. Casey et al., Proc. Natl. Acad. Sci. U.S.A. 97,
8728 (2000).
21. C. S. Carter et al., Proc. Natl. Acad. Sci. U.S.A. 97,
1944 (2000).
National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, and the
National Cancer Institute. We thank our volunteers,
K. Amunts for helpful anatomical discussions, and the
radiographers at the Research Center Jülich for technical assistance.
Supporting Online Material
www.sciencemag.org/cgi/content/full/301/5631/384/DC1
Materials and Methods
References
Downloaded from www.sciencemag.org on January 12, 2009
ed) during visuospatial decisions. Note the specificity of this result: Even when the threshold was
reduced to P # 0.05, uncorrected, no other significant clusters were found throughout the brain.
(B) This schema summarizes the negative findings for right ACC: As indicated by the gray dashed
lines, right ACC shows no context-dependent contributions to any left-hemispheric area during
visuospatial decisions and none to any left- or right-hemispheric area at all during letter decisions.
Norm of reaction: Example #1
Influence of Life Stress on
Depression: Moderation by a
Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2*
Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2
Joseph McClay,1 Jonathan Mill,1 Judy Martin,3
Antony Braithwaite,4 Richie Poulton3
References and Notes
1. J. L. Bradshaw, N. C. Nettleton, Behav. Brain Sci. 4, 51
(1981).
2. J. B. Hellige, Annu. Rev. Psychol. 41, 55 (1990).
3. J. C. Marshall, Behav. Brain Sci. 4, 72 (1981).
4. K. Hugdahl, R. J. Davidson, The Asymmetrical Brain
(MIT Press, Cambridge, MA, 2003).
5. J. Sergent, Psychol. Bull. 93, 481 (1983).
6. C. Chiarello, J. Senehi, M. Soulier, Neuropsychologia 4,
521 (1986).
7. P. M. Corballis, M. G. Funnell, M. S. Gazzaniga, NeuroReport 10, 2183 (1999).
8. C. J. Price, R. J. S. Wise, R. S. J. Frackowiak, Cereb.
Cortex 6, 62 (1996).
9. G. R. Fink et al., Nature 382, 626 (1996).
10. L. E. Nystrom et al., Neuroimage 11, 424 (2000).
11. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,
Cereb. Cortex 6, 39 (1996).
12. J. Levy, C. Trevarthen, J. Exp. Psychol. Hum. Percept.
Perform. 2, 299 (1976).
13. M. S. Gazzaniga, Brain 123, 1293 (2000).
14. M. I. Posner, S. E. Petersen, Annu. Rev. Neurosci. 13,
25 (1990).
15. T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
16. R. Desimone, J. Duncan, Annu. Rev. Neurosci. 18, 193
(1995).
17. Materials and methods are available as supporting
material on Science Online.
18. Using a 2 ! 2 ! 2 factorial design, with letter vs.
visuospatial decisions, left vs. right visual fields of
presentation, and left vs. right response hand as the
three experimental factors, the eight conditions occurred equally often and were varied systematically
as blocked conditions in a pseudorandom fashion.
386
23 April 2003; accepted 6 June 2003
In a prospective-longitudinal study of a representative birth cohort, we tested
why stressful experiences lead to depression in some people but not in others.
A functional polymorphism in the promoter region of the serotonin transporter
(5-HT T) gene was found to moderate the influence of stressful life events on
depression. Individuals with one or two copies of the short allele of the 5-HT T
promoter polymorphism exhibited more depressive symptoms, diagnosable
depression, and suicidality in relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual’s response
to environmental insults is moderated by his or her genetic makeup.
Depression is among the top five leading causes
of disability and disease burden throughout the
world (1). Across the life span, stressful life
events that involve threat, loss, humiliation, or
defeat influence the onset and course of depresMedical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College London, PO80 De Crespigny Park,
London, SE5 8AF, UK. 2Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3Dunedin School of Medicine, 4Department of Pathology,
University of Otago, Dunedin, New Zealand.
1
*To whom correspondence should be addressed. Email: t.moffitt@iop.kcl.ac.uk
sion (2–5). However, not all people who encounter a stressful life experience succumb to
its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup (6, 7). Behavioral genetics research supports this prediction, documenting
that the risk of depression after a stressful event
is elevated among people who are at high genetic risk and diminished among those at low
genetic risk (8). However, whether specific
genes exacerbate or buffer the effect of stressful
life events on depression is unknown. In this
study, a functional polymorphism in the pro-
s = allele for
“short” serotonin
transporter
l = allele for
“long” serotonin
transporter
18 JULY 2003 VOL 301 SCIENCE www.sciencemag.org
Fig. 1. Results of multiple regression analyses estimating the associati
tivity (25) that investigated two tasks with right
hemisphere dominance demonstrated top-down
effects that were specific for the right hemisphere, i.e., from the right middle frontal gyrus
(area 46) on right extrastriate areas. It is thus
likely that our findings generalize to other lateralized tasks. Although we cannot exclude lateralization contingent on stimulus type in some
situations, our results are consistent with previous findings from split-brain patient studies (7)
and positron emission tomography (11) showing
hemispheric specialization based on task demands. Research on hemispheric specialization
should move beyond analyses of asymmetric
regional activations and focus more strongly on
functional interactions within and between
hemispheres.
19. A. W. MacDonald, J. D. Cohen, V. A. Stenger, C. S.
Carter, Science 288, 1835 (2000).
20. B. J. Casey et al., Proc. Natl. Acad. Sci. U.S.A. 97,
8728 (2000).
21. C. S. Carter et al., Proc. Natl. Acad. Sci. U.S.A. 97,
1944 (2000).
National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, and the
National Cancer Institute. We thank our volunteers,
K. Amunts for helpful anatomical discussions, and the
radiographers at the Research Center Jülich for technical assistance.
Supporting Online Material
www.sciencemag.org/cgi/content/full/301/5631/384/DC1
Materials and Methods
References
Downloaded from www.sciencemag.org on January 12, 2009
ed) during visuospatial decisions. Note the specificity of this result: Even when the threshold was
reduced to P # 0.05, uncorrected, no other significant clusters were found throughout the brain.
(B) This schema summarizes the negative findings for right ACC: As indicated by the gray dashed
lines, right ACC shows no context-dependent contributions to any left-hemispheric area during
visuospatial decisions and none to any left- or right-hemispheric area at all during letter decisions.
Norm of reaction: Example #1
Influence of Life Stress on
Depression: Moderation by a
Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2*
Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2
Joseph McClay,1 Jonathan Mill,1 Judy Martin,3
Antony Braithwaite,4 Richie Poulton3
References and Notes
1. J. L. Bradshaw, N. C. Nettleton, Behav. Brain Sci. 4, 51
(1981).
2. J. B. Hellige, Annu. Rev. Psychol. 41, 55 (1990).
3. J. C. Marshall, Behav. Brain Sci. 4, 72 (1981).
4. K. Hugdahl, R. J. Davidson, The Asymmetrical Brain
(MIT Press, Cambridge, MA, 2003).
5. J. Sergent, Psychol. Bull. 93, 481 (1983).
6. C. Chiarello, J. Senehi, M. Soulier, Neuropsychologia 4,
521 (1986).
7. P. M. Corballis, M. G. Funnell, M. S. Gazzaniga, NeuroReport 10, 2183 (1999).
8. C. J. Price, R. J. S. Wise, R. S. J. Frackowiak, Cereb.
Cortex 6, 62 (1996).
9. G. R. Fink et al., Nature 382, 626 (1996).
10. L. E. Nystrom et al., Neuroimage 11, 424 (2000).
11. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,
Cereb. Cortex 6, 39 (1996).
12. J. Levy, C. Trevarthen, J. Exp. Psychol. Hum. Percept.
Perform. 2, 299 (1976).
13. M. S. Gazzaniga, Brain 123, 1293 (2000).
14. M. I. Posner, S. E. Petersen, Annu. Rev. Neurosci. 13,
25 (1990).
15. T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
16. R. Desimone, J. Duncan, Annu. Rev. Neurosci. 18, 193
(1995).
17. Materials and methods are available as supporting
material on Science Online.
18. Using a 2 ! 2 ! 2 factorial design, with letter vs.
visuospatial decisions, left vs. right visual fields of
presentation, and left vs. right response hand as the
three experimental factors, the eight conditions occurred equally often and were varied systematically
as blocked conditions in a pseudorandom fashion.
386
23 April 2003; accepted 6 June 2003
In a prospective-longitudinal study of a representative birth cohort, we tested
why stressful experiences lead to depression in some people but not in others.
A functional polymorphism in the promoter region of the serotonin transporter
(5-HT T) gene was found to moderate the influence of stressful life events on
depression. Individuals with one or two copies of the short allele of the 5-HT T
promoter polymorphism exhibited more depressive symptoms, diagnosable
depression, and suicidality in relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual’s response
to environmental insults is moderated by his or her genetic makeup.
Depression is among the top five leading causes
of disability and disease burden throughout the
world (1). Across the life span, stressful life
events that involve threat, loss, humiliation, or
defeat influence the onset and course of depresMedical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College London, PO80 De Crespigny Park,
London, SE5 8AF, UK. 2Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3Dunedin School of Medicine, 4Department of Pathology,
University of Otago, Dunedin, New Zealand.
1
*To whom correspondence should be addressed. Email: t.moffitt@iop.kcl.ac.uk
sion (2–5). However, not all people who encounter a stressful life experience succumb to
its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup (6, 7). Behavioral genetics research supports this prediction, documenting
that the risk of depression after a stressful event
is elevated among people who are at high genetic risk and diminished among those at low
genetic risk (8). However, whether specific
genes exacerbate or buffer the effect of stressful
life events on depression is unknown. In this
study, a functional polymorphism in the pro-
18 JULY 2003 VOL 301 SCIENCE www.sciencemag.org
ssion analyses estimating the association between number of
Fig. 2. Results of regres
s = association
allele for betwe
the
“short”
serotonin
ment
(between
the age
transporter
adult
depression (ages
of 5-HT T genotype. A
l = allele for
mozygotes,
92 (63%),
“long”members
serotonin
study
were i
probable
maltreatmen
transporter
ment groups, respectiv
heterozygotes, 286 (66
(8%) were in the no
maltreatment groups.
mozygotes, 172 (65%)
tivity (25) that investigated two tasks with right
hemisphere dominance demonstrated top-down
effects that were specific for the right hemisphere, i.e., from the right middle frontal gyrus
(area 46) on right extrastriate areas. It is thus
likely that our findings generalize to other lateralized tasks. Although we cannot exclude lateralization contingent on stimulus type in some
situations, our results are consistent with previous findings from split-brain patient studies (7)
and positron emission tomography (11) showing
hemispheric specialization based on task demands. Research on hemispheric specialization
should move beyond analyses of asymmetric
regional activations and focus more strongly on
functional interactions within and between
hemispheres.
19. A. W. MacDonald, J. D. Cohen, V. A. Stenger, C. S.
Carter, Science 288, 1835 (2000).
20. B. J. Casey et al., Proc. Natl. Acad. Sci. U.S.A. 97,
8728 (2000).
21. C. S. Carter et al., Proc. Natl. Acad. Sci. U.S.A. 97,
1944 (2000).
National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, and the
National Cancer Institute. We thank our volunteers,
K. Amunts for helpful anatomical discussions, and the
radiographers at the Research Center Jülich for technical assistance.
Supporting Online Material
www.sciencemag.org/cgi/content/full/301/5631/384/DC1
Materials and Methods
References
Downloaded from www.sciencemag.org on January 12, 2009
ed) during visuospatial decisions. Note the specificity of this result: Even when the threshold was
reduced to P # 0.05, uncorrected, no other significant clusters were found throughout the brain.
(B) This schema summarizes the negative findings for right ACC: As indicated by the gray dashed
lines, right ACC shows no context-dependent contributions to any left-hemispheric area during
visuospatial decisions and none to any left- or right-hemispheric area at all during letter decisions.
Norm of reaction: Example #1
Influence of Life Stress on
Depression: Moderation by a
Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2 Karen Sugden,1 Terrie E. Moffitt,1,2*
Alan Taylor,1 Ian W. Craig,1 HonaLee Harrington,2
Joseph McClay,1 Jonathan Mill,1 Judy Martin,3
Antony Braithwaite,4 Richie Poulton3
References and Notes
1. J. L. Bradshaw, N. C. Nettleton, Behav. Brain Sci. 4, 51
(1981).
2. J. B. Hellige, Annu. Rev. Psychol. 41, 55 (1990).
3. J. C. Marshall, Behav. Brain Sci. 4, 72 (1981).
4. K. Hugdahl, R. J. Davidson, The Asymmetrical Brain
(MIT Press, Cambridge, MA, 2003).
5. J. Sergent, Psychol. Bull. 93, 481 (1983).
6. C. Chiarello, J. Senehi, M. Soulier, Neuropsychologia 4,
521 (1986).
7. P. M. Corballis, M. G. Funnell, M. S. Gazzaniga, NeuroReport 10, 2183 (1999).
8. C. J. Price, R. J. S. Wise, R. S. J. Frackowiak, Cereb.
Cortex 6, 62 (1996).
9. G. R. Fink et al., Nature 382, 626 (1996).
10. L. E. Nystrom et al., Neuroimage 11, 424 (2000).
11. S. M. Courtney, L. G. Ungerleider, K. Keil, J. V. Haxby,
Cereb. Cortex 6, 39 (1996).
12. J. Levy, C. Trevarthen, J. Exp. Psychol. Hum. Percept.
Perform. 2, 299 (1976).
13. M. S. Gazzaniga, Brain 123, 1293 (2000).
14. M. I. Posner, S. E. Petersen, Annu. Rev. Neurosci. 13,
25 (1990).
15. T. Shallice, From Neuropsychology to Mental Structure (Cambridge Univ. Press, Cambridge, 1988).
16. R. Desimone, J. Duncan, Annu. Rev. Neurosci. 18, 193
(1995).
17. Materials and methods are available as supporting
material on Science Online.
18. Using a 2 ! 2 ! 2 factorial design, with letter vs.
visuospatial decisions, left vs. right visual fields of
presentation, and left vs. right response hand as the
three experimental factors, the eight conditions occurred equally often and were varied systematically
as blocked conditions in a pseudorandom fashion.
386
23 April 2003; accepted 6 June 2003
In a prospective-longitudinal study of a representative birth cohort, we tested
why stressful experiences lead to depression in some people but not in others.
A functional polymorphism in the promoter region of the serotonin transporter
(5-HT T) gene was found to moderate the influence of stressful life events on
depression. Individuals with one or two copies of the short allele of the 5-HT T
promoter polymorphism exhibited more depressive symptoms, diagnosable
depression, and suicidality in relation to stressful life events than individuals
homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual’s response
to environmental insults is moderated by his or her genetic makeup.
Depression is among the top five leading causes
of disability and disease burden throughout the
world (1). Across the life span, stressful life
events that involve threat, loss, humiliation, or
defeat influence the onset and course of depresMedical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College London, PO80 De Crespigny Park,
London, SE5 8AF, UK. 2Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3Dunedin School of Medicine, 4Department of Pathology,
University of Otago, Dunedin, New Zealand.
1
*To whom correspondence should be addressed. Email: t.moffitt@iop.kcl.ac.uk
sion (2–5). However, not all people who encounter a stressful life experience succumb to
its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup (6, 7). Behavioral genetics research supports this prediction, documenting
that the risk of depression after a stressful event
is elevated among people who are at high genetic risk and diminished among those at low
genetic risk (8). However, whether specific
genes exacerbate or buffer the effect of stressful
life events on depression is unknown. In this
study, a functional polymorphism in the pro-
18 JULY 2003 VOL 301 SCIENCE www.sciencemag.org
Fig. 2. Results of regression analysis estimating
s = allele for
“short” serotonin
transporter
l = allele for
“long” serotonin
transporter
Norm of Reaction
•
Even when there is a substantial genetic
contribution to a psychological trait, the amount of
variation in the trait that is explained by genetic
similarity (i.e., heritability) depends on the
subjects’ environment
PSYCHOLOGICAL SCIENCE
Norm of reaction: Example #2
•
•
Turkheimer et al.
(2003) calculated IQ
heritability for twins
who differed in SES
Sample median
family income
$22,000 (in 1997
dollars); 1997 US
median $53,000
Fig. 3. Proportion of total Full-Scale IQ variance accounted for by A, C, and E plotted as a function of obser
Norm of Reaction
•
•
Does the norm of reaction imply that nature’s role is
somehow arbitrary, uncertain, or unreal?
Consider PKU disorder
In 100% of cases, the defective allele creates a defective enzyme
that is from 0-50% effective as normal in breaking down
phenylalanine
In 100% of cases the build up of phenylalanine is poisonous to
the brain and results in severe mental retardation
Norm of reaction still applies:
In an environment with NO phenylalanine, the defective
gene won’t make any difference in behavior
In an environment WITH phenylalanine, the gene will
make a huge difference in behavior
•
•
•
•
•
4. Child’s Phenotype—Child’s
Environment
4. Child’s Phenotype—Child’s
Environment
•
Children are active sources of
their own development in two
ways:
They actively evoke certain
responses from others (e.g., calm,
beautiful babies)
They actively select surroundings
and experiences conducive to
their innate interests, talents, and
personality characteristics.
h2 + e2 ≠ 1
•
•
•
Developmental Neuroscience
•
•
So far we’ve been talking about genes that vary
from person to person, but genes shared by
(virtually) all people do a lot of work
recipe for bodies
recipe for brains
Developmental neuroscience is interested in the
recipe (and cooking) of the nervous system
•
•