Foetal testosterone and
autistic traits
Simon Baron-Cohen
Cambridge University
Autism Research Centre
Collaborators

Psychology and Brain Scanning


Sally Wheelwright, Johnny Lawson, Nigel Goldenfeld, Jen Richler,
Jen Connellan, Anna Bakti, Carrie Allison, Ed Bullmore, Howard
Ring, Xavier Chitnis
Hormones

Gerald Hackett, Kevin Taylor, Rebecca Knickmeyer, Bonnie
Auyeung, Emma Chapman, Svetlana Lutchmaya, Melissa Hines,
Why the foetal androgen theory?

Autism sex ratio (4: 1); Asperger Syndrome (9:1)

Male foetuses produce twice as much testosterone
and individual differences are 20-fold

Testosterone has organizational effects on brain
development

“The autistic personality is an extreme variant of
male intelligence” (Hans Asperger, 1944)
Sex differences in the human brain
Males > Females
 INAH
(interstitial nuclei of
the anterior hypothalamus)
 Amygdala
 Planum parietale
 Planum temporale
Females > Males
 BST
(bed nucleus of the
stria terminalis, hypothalamus)
 Corpus callosum
 Anterior commissure
From Hines 2003
Spontaneous Toy Choice
vehicles, constructional
Dolls, emotional stories
Hines 2003
Spontaneous toy choice: monkeys
Alexander and Hines 2002
maths, computing, physics,
engineering, tool-making
Primary
school
teaching,
counselling
SAT-Maths 1972-97
Empathizing and Systemizing

Empathizing (E)



The drive to identify another person’s thoughts and
feelings
and respond to these with an appropriate emotion
Systemizing (S)


The drive to analyse a system, or to build a system
Mechanical, abstract, natural, collectible
sarcastic
stern
suspicious
x
sd
dispirited
Female
Male
AS
22.1
(2.0)
19.5
(2.6)
16.6
(2.9)
JCPP
1997
Intuitive Physics Test
Males
28.0
(10.9)
Females
16.2
(9.3)
AS
16.3
(3.1)
Controls
10.3
(2.8)
JADD, 2004
Int J. Learning
Dis, 2001
Attention to detail:
Prerequisite for systemizing
Females
66.7
(36.7)
Males
46.2
(20.5)
JCN, 1997
AS
32.2
(27.0)
EFT > males
fMRI studies: females
Embedded
Figures
Test
Eyes Test
Brain and Cog (2006)
Genetics: Embedded Figures Test
Males
Females
x
46.2
66.7
sd
20.5
36.7
AS
Fathers
Mothers
32.2
32.8
48.6
27.0
17.7
31.8
JCN, 1997
Genetics:
Eyes Test
Males
Females
AS
x
19.5
22.1
16.6
sd
2.6
2.0
2.9
Fathers
Mothers
17.3
18.9
1.6
2.1
sarcastic
stern
suspicious
dispirited
JCN, JCPP (1997)
Innate sex
differences?
Infant Behavior and
Dev (2000)
Boys
Girls
Face
25
36
Mobile
43
17
Equal
32
47
A 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 levels
Hines (2003)
Follow-up studies

12-19 weeks gestation: amnio

12-24 months: eye contact, vocab

48 months: social relationships

8 yrs: empathy, systemizing
embedded figures test
 autistic traits

Mean number of eye contact episodes over 20 min.
26
24
Looking up at the face
during a 10 minute
play session
22
20
18
16
14
12
male
female
Eye contact
at 12m
Infant Behav. & Dev. 2002
320
300
280
Which of these words does
your child know and produce?
260
240
220
200
180
160
Mean vocabulary sizemale
female
SEX
Vocabulary
size at 24m
Infant Behav. & Dev. 2002
Feeling sorry
bored
interested
joking
Hidden ‘tent’ figure
Embedded
Figures Test
at 8 years old
Auyeung et al, submitted
Find the target shape as
quickly as you can
The Child AQ
(Autism Spectrum Quotient)
My child prefers to do things with others
rather than on his/her own.
My child prefers to do things the same way
over and over again.
My child frequently gets so strongly absorbed
in one thing that s/he loses sight of other
things.
FT and
autistic
traits
(AQ)
46 to 50
41 to 45
36 to 40
31 to 35
26 to 30
21 to 25
16 to 20
11 to 15
6 to 10
0 to 5
% of subjects
35
30
25
20
15
AS/HFA
Controls
10
5
0
JADD, 2001
Auyeung et al,
submitted
Other clues for the foetal
androgen theory of autism

Timing of puberty


Early puberty in boys with autism (Tordjeman et al, 1997);
delayed menarche in women with AS, and their mothers
(Ingudomnukul et al, 2007)
Lower 2D:4D ratio in autism, AS, sibs and parents
(Manning et al 2001)

Congenital Adrenal Hyperplasia and AQ
CAH females
Typical males
Unaffected sisters
18.4
18.8
16.0
(Knickmeyer et al, 2006)
(5.5)
(6.2)
(4.3)
Conclusions
Foetal testosterone is associated
with psychological sex differences

 Autism
spectrum conditions may fit
an extreme of the typical male brain
Testosterone, and the genes that
control it, may be important in autism

For more information
www.autismresearchcentre.com
Thanks to:
The Nancy Lurie Marks Foundation
Medical Research Council UK
Target Autism Genome
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 empathy
(EQ) at 8 yrs
Social Neurosci 2006
My child likes to collect things
My child is interested in different
types of vehicles
FT and systemizing
at 8 yrs
Euro J Endocrin 2006
The Eyes Test:
Eyesbrain
Task activity
bilateral
inferior
frontal
SSQ ratio
Average SSQ ratio, by group, in Eyes task (4 group
trend)
0.08
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
Fem ales
Left MTG
Left DLPFC
Males
Mothers
Fathers
Group
Brain and Cog (2006)
EFT
Embedded Figures Test: brain activity
left
fusiform
& visual
cortex
Average SSQ ratio, by group, in Embedded Figures task (4
group trend)
0.3
red:
left
SSQ ratio
blue:
right
visual
cortex
0.25
0.2
Le ft vi sua l corte x
Ri g ht vi sua l corte
0.15
0.1
0.05
0
Fem ales
Males
Mothers
Fathers
Group
Brain and Cog (2006)
Grandfathers’ occupations
Engineering
(%)
Social Work
(%)
Autism
21.2
0.5
Downs
10.0
2.5
Autism, 1997
Pathways in testosterone synthesis