Nature and Nurture: Mental Health and Illness Robert Plomin Institute of Psychiatry London

Nature?(genetics)

Nurture?(environment)

Nature u Nature + Nurture = 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 Psychiatry King’s College London Denmark Hill

Institute of Psychiatry Maudsley Hospital 300 PhD students, 50 postdocs 10 departments including Social, Genetic and Developmental Psychiatry Centre

Eliot Slater Eliot Slater 1959: MRC unit in psychiatric genetics 1971: first psychiatric genetics text 1953: first twin research

Social Genetic Developmental Social, Genetic and Developmental Psychiatry (SGDP) Centre

Nature and nurture: How do we know? Does it run in families? –Does not prove nature – could be nurture.

Nature and nurture: 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)

Psychoses Schizophrenia Mood disorders Unipolar depression Bipolar (manic-depression)

Unrelated (population risk) (0%) Second- degree (25%) First- degree (50%) Fraternal twins (50%) Identical twins (100%) Schizophrenia Risk 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)

Risk (%) First-degree relatives Population Unipolar major depression Bipolar disorder 9% 3% Family studies of mood disorders 8% 1% PopulationFirst-degree relatives

Twin studies of mood disorders Major depressionBipolar depression Twin Concordance (%)

DZ Plomin et al. (1994) Science Alcoholism (females) Twin Probandwise concordance Alcoholism (males) Alzheimer’s disease Autism Reading disability MZMZ Hyperactivity Twin studies of other mental illnesses

MZDZ Plomin et al. (1994) Science Parkinson’s disease Twin Probandwise concordance Breast cancer Hypertension Ischemic heart disease Rheumatoid arthritis Peptic ulcer Chronic obstructive Pulmonary disorder Idiopathic epilepsy Twin studies of common medical disorders

Perceptions of nature/nurture: % indicating that genes are at least as important as environment (Walker & Plomin, 2005) 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)

TEDS twins (~7500 pairs)

TEDS 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:

SocialNonsocial Social versus nonsocial ASD are different genetically Genetic correlation =.21

Implications Diagnosis – Two different disorders Molecular genetics – different genes for social and nonsocial SN

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 Gene 1903: the word ‘gene’1903: the word ‘gene’ 1953: structure of DNA1953: structure of DNA n 2003: the human DNA sequence n 2053: ???

Human genome sequences 3 billion DNA base pairs 3 billion DNA base pairs 3 million DNA differences (>1% frequency) 3 million DNA differences (>1% frequency)

Finding genes Some replicated linkages and associations –Schizophrenia –Reading disability –Hyperactivity –Autism –Dementia Slower progress than expected

Finding genes: What are we looking for? Answer: many QTLs of very small effect

Diagnostic threshold Rare single-gene disorders

Diagnostic threshold The quantitative trait locus (QTL) model for common complex disorders

Schizophrenia linkage and association: Dysbindin (DTNBP1) and neuregulin 1 (NRG1) Owen et al. (2005) Trends in Genetics 21:

Replicated linkages for reading disability DCDC2 Fisher & DeFries (2002) Nature 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)