foetal testosterone and autistic traits simon baron-cohen cambridge university autism research...
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Foetal testosterone and autistic traits
Foetal testosterone and autistic traits
Simon Baron-CohenSimon Baron-Cohen
Cambridge UniversityCambridge University
Autism Research CentreAutism Research Centre
CollaboratorsCollaborators
Psychology and Brain ScanningPsychology and Brain Scanning Sally Wheelwright, Johnny Lawson, Nigel Goldenfeld, Jen Sally Wheelwright, Johnny Lawson, Nigel Goldenfeld, Jen
Richler, Jen Connellan, Anna Bakti, Carrie Allison, Ed Bullmore, Richler, Jen Connellan, Anna Bakti, Carrie Allison, Ed Bullmore, Howard Ring, Xavier ChitnisHoward Ring, Xavier Chitnis
HormonesHormones Gerald Hackett, Kevin Taylor, Rebecca Knickmeyer, Bonnie Gerald Hackett, Kevin Taylor, Rebecca Knickmeyer, Bonnie
Auyeung, Emma Chapman, Svetlana Lutchmaya, Melissa Hines, Auyeung, Emma Chapman, Svetlana Lutchmaya, Melissa Hines,
Why the foetal androgen theory?Why the foetal androgen theory?
Autism sex ratio (4: 1); Asperger Syndrome (9:1)Autism sex ratio (4: 1); Asperger Syndrome (9:1)
Male foetuses produce twice as much testosterone Male foetuses produce twice as much testosterone and individual differences are 20-foldand individual differences are 20-fold
Testosterone has organizational effects on brain Testosterone has organizational effects on brain developmentdevelopment
““The autistic personality is an extreme variant of The autistic personality is an extreme variant of male intelligence” (Hans Asperger, 1944)male intelligence” (Hans Asperger, 1944)
Males > FemalesMales > Females INAH (interstitial nuclei of INAH (interstitial nuclei of the anterior hypothalamus)the anterior hypothalamus) AmygdalaAmygdala Planum parietalePlanum parietale Planum temporalePlanum temporale
Sex differences in the human brainSex differences in the human brain
Females > Males Females > Males BST (bed nucleus of the BST (bed nucleus of the stria terminalis, hypothalamus)stria terminalis, hypothalamus) Corpus callosumCorpus callosum Anterior commissureAnterior commissure From Hines 2003
vehicles, constructional
Dolls, emotional stories Hines 2003
Spontaneous Toy Choice
Spontaneous toy choice: monkeysSpontaneous toy choice: monkeys
Alexander and Hines 2002
maths, computing, physics,engineering, tool-making
Primary school teaching, counselling
SAT-Maths 1972-97
Empathizing and SystemizingEmpathizing and Systemizing
Empathizing (E)Empathizing (E) The drive to identify another person’s thoughts and The drive to identify another person’s thoughts and
feelingsfeelings and respond to these with an appropriate emotionand respond to these with an appropriate emotion
Systemizing (S) Systemizing (S) The drive to analyse a system, or to build a systemThe drive to analyse a system, or to build a system Mechanical, abstract, natural, collectibleMechanical, abstract, natural, collectible
sarcastic stern
suspicious dispirited
FemaleFemale MaleMale ASAS
xx 22.122.1 19.5 19.5 16.616.6
sdsd (2.0)(2.0) (2.6)(2.6) (2.9)(2.9) JCPP1997
Intuitive Physics Test
MalesMales FemalesFemales28.028.0 16.216.2(10.9)(10.9) (9.3)(9.3)
ASAS ControlsControls
16.316.3 10.310.3
(3.1)(3.1) (2.8)(2.8)
JADD, 2004Int J. LearningDis, 2001
FemalesFemales MalesMales ASAS
66.766.7 46.246.2 32.232.2
(36.7)(36.7) (20.5)(20.5) (27.0)(27.0)
JCN, 1997
Attention to detail: Prerequisite for systemizing
EFT
Brain and Cog (2006)
Eyes Test
EmbeddedFiguresTest
fMRI studies: females > males
Genetics: Embedded Figures TestGenetics: Embedded Figures Test
xx sdsd
MalesMales 46.2 46.2 20.520.5
FemalesFemales 66.766.7 36.736.7
ASAS 32.232.2 27.027.0
FathersFathers 32.832.8 17.717.7
MothersMothers 48.648.6 31.831.8JCN, 1997
Genetics:Eyes TestGenetics:Eyes Test
xx sdsd
MalesMales 19.519.5 2.62.6
FemalesFemales 22.122.1 2.0 2.0
ASAS 16.616.6 2.92.9
FathersFathers 17.317.3 1.61.6
MothersMothers 18.918.9 2.12.1 JCN, JCPP (1997)
sarcasticsternsuspiciousdispirited
Innate sex differences?Innate sex differences?
FaceFace MobileMobile EqualEqual
BoysBoys 2525 4343 3232
Girls Girls 3636 1717 4747
Infant Behavior and Dev (2000)
A window into foetal testosterone:amniocentesisA window into foetal testosterone:amniocentesis
Injection of FT masculinizes female rat brain and behaviour
Produced by testes and adrenal glands, crosses blood brain barrier
Binds to androgen receptors in cytoplasm, modulates serotonin and GABA, and prevents apoptosis
3 surges in T levels3 surges in T levels
Hines (2003)
Follow-up studiesFollow-up studies
12-19 weeks gestation: amnio12-19 weeks gestation: amnio
12-24 months: eye contact, vocab12-24 months: eye contact, vocab
48 months: social relationships48 months: social relationships
8 yrs: empathy, systemizing 8 yrs: empathy, systemizing embedded figures testembedded figures test autistic traitsautistic traits
Eye contact
at 12m
Eye contact
at 12m
femalemaleMean number of eye contact episodes over 20 min.
26
24
22
20
18
16
14
12
Infant Behav. & Dev. 2002
Looking up at the face during a 10 minute play session
Vocabularysize at 24mVocabularysize at 24m
SEX
femalemaleMean vocabulary size
320
300
280
260
240
220
200
180
160
Infant Behav. & Dev. 2002
Which of these words doesyour child know and produce?
Feeling sorry
interested
bored
joking
Hidden ‘tent’ figure Hidden ‘tent’ figure
Embedded Figures Testat 8 years old
Auyeung et al, submitted
Find the target shape asquickly as you can
The Child AQ (Autism Spectrum Quotient)The Child AQ (Autism Spectrum Quotient)My child prefers to do things with others My child prefers to do things with others
rather than on his/her own. rather than on his/her own.
My child prefers to do things the same way My child prefers to do things the same way over and over again. over and over again.
My child frequently gets so strongly absorbed My child frequently gets so strongly absorbed in one thing that s/he loses sight of other in one thing that s/he loses sight of other things. things.
FT andautistic traits(AQ)
FT andautistic traits(AQ)
0
5
10
15
20
25
30
35
0 to 56 to 1011 to 1516 to 2021 to 2526 to 3031 to 3536 to 4041 to 4546 to 50
% of subjects
AS/HFAControls
JADD, 2001Auyeung et al, submitted
Other clues for the foetal androgen theory of autismOther clues for the foetal androgen theory of autism Timing of pubertyTiming of puberty
Early puberty in boys with autism (Tordjeman et al, 1997); delayed Early puberty in boys with autism (Tordjeman et al, 1997); delayed menarche in women with AS, and their mothers (Ingudomnukul et al, menarche in women with AS, and their mothers (Ingudomnukul et al, 2007)2007)
Lower 2D:4D ratio in autism, AS, sibs and parents Lower 2D:4D ratio in autism, AS, sibs and parents (Manning et al 2001)(Manning et al 2001)
Congenital Adrenal Hyperplasia and AQ Congenital Adrenal Hyperplasia and AQ (Knickmeyer et al, 2006)(Knickmeyer et al, 2006)CAH femalesCAH females 18.418.4 (5.5)(5.5)Typical malesTypical males 18.818.8 (6.2)(6.2)Unaffected sisters Unaffected sisters 16.016.0 (4.3)(4.3)
ConclusionsConclusions Foetal testosterone is associated Foetal testosterone is associated with psychological sex differenceswith psychological sex differences
Autism spectrum conditions may fit Autism spectrum conditions may fit an extreme of the typical male brainan extreme of the typical male brain
Testosterone, and the genes that Testosterone, and the genes that control it, may be important in autismcontrol it, may be important in autism
www.autismresearchcentre.com
For more information
Thanks to: The Nancy Lurie Marks Foundation
Medical Research Council UKTarget Autism Genome
FT and empathy (EQ) at 8 yrs
Social Neurosci 2006
My child would worry about how
another child would feel if they
weren’t invited to a party
My child gets upset at seeing others
crying or in pain
FT and systemizingat 8 yrs
Euro J Endocrin 2006
My child likes to collect things
My child is interested in different
types of vehicles
bilateralinferior frontal
Eyes TaskThe Eyes Test: brain activity
Brain and Cog (2006)
EFT
leftfusiform& visualcortex
Embedded Figures Test: brain activity
Brain and Cog (2006)
red:left
blue:rightvisualcortex
Grandfathers’ occupationsGrandfathers’ occupations
EngineeringEngineering Social Work Social Work
(%)(%) (%)(%)
Autism Autism 21.221.2 0.50.5
DownsDowns 10.010.0 2.52.5
Autism, 1997
Pathways in testosterone synthesis
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