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)