ADHD Netwerk Meeting, 16th June 2016
ThenatureandnurtureofADHD–
adevelopmentalperspec7ve
CorinaGreven,PhD
Overview
1.  Introduc7ontothenature-nurturedebate
2.  ThenatureandnurtureofADHD
3.  Developmentalaspects
4.  Nature-nurturemisunderstandings
%whothinknature(genes)isatleastas
importantasnurture(environments)
Walker & Plomin, 2005
Nature–nurturecontroversy
• Oneofoldestdebates
• Un$l1960s:Viewinfavourofnurturedominated(e.g.schizophrenogenic
mother)
• Now:Notgenesversusenvironments
genesandenvironments!
• Howdoweknow?
Quan7ta7vegene7cs
• Es7matesheritability.
• Asmuchstudyofgenesasofenvironments.
Quantitative Genetic
Research Designs
Family Design
Adoption Design
e.g.,
First degree
relatives
e.g.,
Larger family
pedigrees
Adoptive vs.
non-adoptive
relatives
Twin Design
e.g.,
Mono- vs.
dizygotic
twins
IVF Design
e.g.,
Twins apart
and
together
Parents who
differ in
genetic
relatedness
Twinstudies
Monozygo'c(MZ)
Gene'csimilarity=100%
Dizygo'c(DZ)
Gene'csimilarity=50%
• Logic:IfMZmoresimilarthanDZtwinsàtraitmustbegene7cally
influenced(=heritable)
Twinstudies
• Es7matethecontribu7onofgene7candenvironmentalfactorstoindividual
differences(variance)inatrait.
• Wetypicallyes7mate:
MZ 100%
•  A:Addi7vegene7cs(heritability)
A
DZ 50%
•  C:Common(shared)environment
C
MZ 100%
DZ 100%
MZ 0%
•  E:Environmentspecifictoeachtwin(non-shared)
E
DZ 0%
• Sharedornon-shared?
•  Divorce?Sharedclassroomenvironment/sharedteacher?
•  Differen7aleffectsof:accidents,percep7onsofenvironment,physical
illness
Overview
1.  Introduc7ontothenature-nurturedebate
2.  ThenatureandnurtureofADHD
3.  Developmentalaspects
4.  Nature-nurturemisunderstandings
TwinstudiesonADHD
A
• HighheritabilityofADHD[1].
C
70% 0% 30%
• Lialeevidenceforae7ological
genderdifferences[2].
• 2dimensions:INATTandHYPIMP[3-4].
E
ADHD
(traits)
.50
A
C
E
A
C
E
70% 0% 30%
70% 0% 30%
INATT
HYP-IMP
[1] Burt 2009 Psychol Bull. [2] Greven submitted Oxford Handbook ADHD. [3] Greven 2011 J Abnorm Psychol.
[4] Nikolas 2010 J Abnorm Psychol.
Twinstudies:otherchildbehaviouralproblems
Trait/disorder
ADHD
Opposi7onal
defiantproblems
Conduct
problems
Depression
Anxiety
Heritability(A)
70%
59%
Shared
Non-shared
environment(C) environment(E)
0%
30%
10%
31%
58%
15%
28%
44%
48%
14%
12%
42%
40%
Meta-analysis: Burt 2009 Psychol Bull
TwinstudiesonADHD:ratereffects
• Modestrateragreement[1].
• Heritabilityparent>teacher>child-report[2].
àsamevsdifferentrater?
• Most(~80%)ofassocia7onbetweenraters
explainedbysharedgenes[2].
A
A
A
80%
60%
50%
ADHDtraits
(parent)
[1] Derks 2006 Behav Genet. [2] Merwood Greven 2012 Psychol Med.
ADHDtraits
(teacher)
ADHDtraits
(child)
WhatgenesexplaintheheritabilityofADHD?
•  Individualgenes
cannotexplainhigh
heritabilityofADHD
Maher 2008 Nature
SNPheritability
• SNP=singlenucleo7depolymorphism
SNPHERITABILITY
Gene'csimilarity
SNPsimilarityofunrelated
individuals
Behaviouralsimilarity
Ifindividualswhoaremoresimilargene,cally,
arealsomoresimilarbehaviourally
àtraitisheritable
• AllSNPsinthegenometogether.Nospecificgenes.
SNPheritability
-4100individualswithADHD
-12000controls
80
70%
60
40
30%
20
0
Twin
heritability
SNP
heritability
ADHD
•  ExplainalmosthalfoftwinheritabilityusingDNA.
Psychiatric Genomics Consortium 2013 Nature Genetics
Overview
1.  Introduc7ontothenature-nurturedebate
2.  ThenatureandnurtureofADHD
3.  Developmentalaspects
4.  Nature-nurturemisunderstandings
HeritabilityofADHDover7me
• Heritabilitydecreases?[1-2]Orstable?[3]
%
100
heritability
80
60
40
20
shared environment
0
ChildhoodAdolescenceAdulthood
[1] Boomsma 2010 Plos One. [2] Larsson 2013 Psychol Med. [3] Larsson 2014 Psychol Med.
HYP-IMP
Gene7ccontribu7onstodevelopmentalcourse
ChildhoodAdolescenceAdulthood
ChildhoodAdolescenceAdulthood
Greven 2011 J Abnorm Psychol.
Gene7ccontribu7onstodevelopmentalcourse
> ½ of influence
not shared
E
A
A
E
(parent-rated)
80% 20%
• >8300twinpairs,popula7on-based.
• Genesexplained80%ofindividual
differencesinchangeofHYP-IMP.
HYP-IMP
• DifferentgenesinvolvedinriskforHYPIMPinchildhood,anddevelopmental
courseintolateadolescence.
age8 1214age16
àHelpsexplainwhysomechildrenwith
ADHDremit,otherspersist.
(= baseline)
Pingault Viding Galera Greven 2015 JAMA Psychiatry
• 90%ofadultslackedchildhooddiagnosisofADHD.
• MayreflectdifferentgenesthanchildhoodADHD.
Whylate-onsetADHD?
• Disordermaybemaskedinchildhood?(protec7vefactors)
• ADHD-likesymptomscausedbyanotherdisorder?
• Adis7nctdisorder?(lowerheritability,morewomen)
Overview
1.  Introduc7ontothenature-nurturedebate
2.  ThenatureandnurtureofADHD
3.  Developmentalaspects
4.  Nature-nurturemisunderstandings
Nature–nurturemisunderstandings:rightor
wrong?
1.  Ifgene7csisimportantforADHD,thereisnothingyoucandoabout
it.
2.  HeritabilityofADHDis70%.Thismeansthedisorderhasgene7c
originsin70%ofindividualswithADHD.
3.  Low es7mates of shared environmental influences on ADHD mean
thatparen7ngdoesnotmaaer.
Nature–nurturemisunderstandings(1)
Ifgene'csisimportant,thereisnothingyoucandoaboutit.(Wrong!)
•  Genesareriskfactors,notdes7ny
•  Weight(diet),phenylkentonuria(diet),ADHD(medica7on,parent
management)
•  QGresearchisabout‘whatis’
•  Notaboutwhat‘couldbe’
•  Notabout‘whatshouldbe’
Nature–nurturemisunderstandings(2)
HeritabilityofADHDis70%àthedisorderhasgene'coriginsin70%of
individualswithADHD.(Wrong!)
•  Heritability
...doesnotrefertoacertainindividual,buttoindividual
differencesinthepopula7on
...es7matesthepropor'onofvariance(=individualdifferences)
inapopula7onaaributabletogene7cdifferences
A
C
E
Nature–nurturemisunderstandings(3)
Lowes'matesofsharedenvironmentalinfluencesmeanthatparen'ng
doesnotma_er.(Wrong!)
• Thereareevidence-basedparen7nginterven7ons(e.g.parent
managementforADHD)
• Gene7cresearchprovidesnewwaysofthinkingabouttheparen7ng
environment(manyenvironmentsareexperienceddifferen7ally)
Takehomemessage
• ADHDis70%heritable.Wecanexplainnearlyhalfofthisheritability
usingDNA(‘SNPheritability’).
• Gene7cfactorsmaybeinvolvedinwhysomeindividualswithADHD
persistwhereasothersremit.
• Heritabilitydoesnotrefertoanindividual,buttoindividual
differencesinthegeneralpopula7on.
• Genesareriskfactors.Evenhighlyheritabledisorderscanbehighly
responsivetoenvironmentalinterven7on.
Thankyouforyoura_en'on!