nature and nurture: mental health and illness robert plomin institute of psychiatry london
TRANSCRIPT
Nature Nature andand Nurture:Nurture:Mental Mental
Health and Health and IllnessIllness
Robert PlominRobert Plomin
Institute of PsychiatryInstitute of Psychiatry
London London
Nature?Nature?(genetics)(genetics)
Nurture?Nurture?(environment(environment
))
Nature Nature + Nurtuure = Controversy
• Nature? Nurture? What do you think?
– Height?– Weight?– Mental illness?
From William Hogarth: ‘The Rakes Progress’ (1735)
1247: Bethlem Hospital (‘bedlam’)1948: Bethlem + Maudsley + IoP
Parliament
Buckingham Palace
Hyde Park
Regent’s Park
Thames
Institute of PsychiatryInstitute of PsychiatryKing’s College LondonKing’s College London
Denmark HillDenmark Hill
Institute of PsychiatryInstitute of Psychiatry
Maudsley HospitalMaudsley Hospital
• 300 PhD students, 50 postdocs • 10 departments including Social, Genetic and Developmental Psychiatry Centre
Social, Genetic and Developmental Psychiatry Social, Genetic and Developmental Psychiatry CentreCentre
Eliot SlaterEliot Slater
1959: MRC unit in psychiatric genetics1959: MRC unit in psychiatric genetics
1971: first psychiatric genetics 1971: first psychiatric genetics texttext
1953: first twin research1953: first twin research
SocialSocial GeneticGenetic
DevelopmentalDevelopmental
Social, Genetic and Developmental Social, Genetic and Developmental Psychiatry (SGDP) CentrePsychiatry (SGDP) Centre
Nature and nurture: Nature and nurture: How do we know?How do we know?
• Does it run in families?– Does not prove nature – could be
nurture.
Nature and nurture: Nature and nurture: How do we know?How do we know?
• Twin studies– Identical twins versus non-identical
twins
• Adoption studies– Nonadoptive versus adoptive
relatives
Identical twins (monozygotic, MZ)
Non-identical, fraternal twins (dizygotic, DZ)
PsychosesPsychoses
• Schizophrenia
• Mood disorders
Unipolar depression
Bipolar (manic-depression)
0
10
20
30
40
50
Unrelated (population risk) (0%)
Second-degree(25%)
First-degree (50%)
Fraternaltwins(50%)
Identical twins (100%)
Sch
izop
hre
nia
Ris
k
Genetic relatedness
1%4%
9%
17%
48%
Genetics and schizophrenia
‘Genain’ quadruplets
Nature and nurture: How do we know?
• Twin studies– Identical twins versus non-identical
twins
• Adoption studies– Nonadoptive versus adoptive
relatives
“Genetic-plus-environmental”relatives
“Genetic”relatives
“Environmental” relatives
Adoption
Adoption studies
Leonard Heston
Schizophrenic parents
Schizophrenic adoptees
Nonschizophrenic parents
Schizophrenic adoptees
7% 0%
Heston’s (1966) adoption study
Psychoses
• Schizophrenia
• Mood disorders
Unipolar depression (major depression)
Bipolar (manic-depression)
0
2
4
6
8
10R
isk
(%
)
First-degreerelatives
Population
Unipolar major depression Bipolar disorder
9%
3%
Family studies of mood disorders
8%
1%
PopulationFirst-degreerelatives
Twin studies of mood disorders
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
MZ DZ MZ DZ
Major depression Bipolar depression
Tw
in C
onco
rdan
ce
Tw
in C
onco
rdan
ce
(%)
(%)
0.0
0.2
0.4
0.6
0.8
1.0
DZ
Plomin et al. (1994) Science
Alcoho
lism
(female
s)
Tw
in P
rob
an
dw
ise
con
cord
an
ce
Alcoho
lism
(male
s)
Alzheim
er’s
disea
seAuti
sm
Readin
g
disab
ility
MZ
Hypera
ctivit
y
Twin studies of other mental illnesses
0.0
0.2
0.4
0.6
0.8
1.0
MZ DZ
Plomin et al. (1994) Science
Parkins
on’s
disea
se
Tw
in P
rob
an
dw
ise
con
cord
an
ce
Breast
canc
er
Hypert
ensio
n
Ische
mic
heart
dise
ase
Rheum
atoid
arthr
itis
Peptic
ulce
r
Chron
ic ob
struc
tive
Pulmon
ary di
sord
er
Idiop
athic
epile
psy
Twin studies of common medical disordersTwin studies of common medical disorders
Perceptions of nature/nurture: % indicating that genes are
at least as important as environment
(Walker & Plomin, 2005)
0 20 40 60 80 100
personality
learning difficulties
mental illness
intelligence
parentsteachers
Percentage with 1-3 responses
Mental illness: nature and nurture
• Importance of nature as well as nurture
• Going beyond nature versus nurture– Development– Multivariate – Nature-nurture interface
language
cognitive
behaviour problems
Twins Early Development Study (TEDS)Twins Early Development Study (TEDS)
TEDS twins (~7500 pairs)TEDS twins (~7500 pairs)
TEDS twins assessed at 2, 3, 4, and 7 yearsTEDS twins assessed at 2, 3, 4, and 7 years
2 years
3 years
7 years
4 years
Mental illness: nature and nurture
• Importance of nature as well as nurture
• Going beyond nature versus nurture– Development– Multivariate – Nature-nurture interface
• ‘Has unusual eye gaze, facial expression or gestures’
• ‘Has at least one good friend’ (reversed item)• ‘Has odd style of communication; old-fashioned,
formal, or pedantic’
• ‘Is extremely distressed by changes to routine or familiar arrangements’
• ‘Has a strong interest in an unusual topic’• ‘Notices small details others might miss’
Autism spectrum disorders (ASD)
Social:
Nonsocial:
Social Nonsocial
Social versus nonsocial ASDare different genetically
Genetic correlation = .21
Implications
• Diagnosis – Two different disorders
• Molecular genetics – different genes for social and nonsocial
S N
Quantitative genetics
• Importance of nature as well as nurture
• Going beyond nature versus nurture– Development– Multivariate – Nature-nurture interface– Molecular genetics: finding DNA
The Century of the GeneThe Century of the Gene
• 1903: the word ‘gene’ 1903: the word ‘gene’ • 1953: structure of DNA1953: structure of DNA
2003: the human 2003: the human DNA sequence DNA sequence
2053: ???2053: ???
Human genome sequenceHuman genome sequencess
• 3 billion DNA base pairs3 billion DNA base pairs
• 3 million DNA differences (>1% 3 million DNA differences (>1% frequency)frequency)
Finding genesFinding genes
• Some replicated linkages and associations – Schizophrenia– Reading disability– Hyperactivity– Autism– Dementia
• Slower progress than expected
Finding genes: What are we looking for?
Major geneMajor gene QTLsQTLs
Answer: many QTLs of very small effect
Diagnostic threshold
Rare single-gene disorders
Diagnostic threshold
The quantitative trait locus (QTL) The quantitative trait locus (QTL) model for common complex model for common complex
disordersdisorders
Schizophrenia linkage and Schizophrenia linkage and association:association:
Dysbindin (DTNBP1) and neuregulin 1 Dysbindin (DTNBP1) and neuregulin 1 (NRG1)(NRG1)
Owen et al. (2005) Trends in Genetics 21:518-525
Replicated linkages for reading Replicated linkages for reading disabilitydisability
DCDC2
Fisher & DeFries (2002) Fisher & DeFries (2002) Nature Reviews NeuroscienceNature Reviews Neuroscience
Microarrays (gene chips): 1 million DNA markers
• DNA routinely collected
• Gene-based diagnoses and treatment programs
• Predicting genetic risk for individuals can lead to prevention
Clinical implications
Implications for research
Nature + Nurture = Controversy
• Not nature versus nurture
• Nature and nurture
Nature - Nurture misunderstandings
• Cannot separate the effects of nature and nurture because both nature and nurture are essential.
Area of a rectangle depends on length and width
Nature - Nurture misunderstandings
• Cannot separate the effects of nature and nurture because both nature and nurture are essential.
• If genetic, nothing you can do about it.
Social concerns?
• changing attitudes of parents about childrearing
• educational and occupational discrimination
• prenatal selection: ‘designer babies’ (in vitro fertilization, normal conceptions, egg donors)