foetal testosterone and autistic traits simon baron-cohen cambridge university autism research...

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