Prof. simon baron cohen מצגת מתוך כנס התפתחות הילד ים המלח 2012 http://www.child-development.org.il/

1. Why is autism more
common in males?
Simon Baron-Cohen
Autism Research Centre
Cambridge University

2. Cambridge-Denmark
Collaborators
Michael V Lombardo, Bonnie Auyeung,
Bhismadev Chakrabarti, Liliana Ruta,
Bent Nørgaard-Pedersen, David
Hougaard, Morsi Abdallah,
Lars Melgard, Arieh Cohen

3. Other 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, Chris
Ashwin, Lindsay Chura, Meng-Chuan Lai, John
Suckling
• Hormones and Genetics
Gerald Hackett, Kevin Taylor, Rebecca Knickmeyer,
Emma Ashwin, Svetlana Lutchmaya, Melissa Hines,
Lindsey Kent, Frank Dudbridge, Erin Ingudomnukul

4. Why the male bias?
•Classic autism: 4:1
•Asperger Syndrome: 9:1
•Social
•Clinical factors
•Genetics
•Hormones (sex steroids/androgens)
•An extreme of certain male-typical traits?

5. Brain Volume
Lenroot & Guidd,
Neuroimage, 2007,
Alonso-
Nancalareset et al,
2008, PNAS
Knickmeyer et al
2008 J Neurosci

6. White Matter
Grey Matter
Lenroot & Guidd, Neuroimage 2007
Gilmore et al (2007) J. Neuroscience.

7. Gray Matter Volume
Lenroot & Guidd, Neuroimage 2007
Temporal
Lobe
Frontal
Lobe

8. females > males
Planum Temporale
(Heschl’s Gyrus)/Wernicke’s)
males > females
Amygdala
Good et al. (2001) Neuroimage

9. Hines (2003)
Child’s Pierce et al (2010)
play

10. Monkey play
Alexander and Hines 2002

11. Occupations
Physics, computer science,
engineering, mathematics
Primary
school,
counseling
Reilly 2012, Plos-One

12. Empathy
Identify another
person’s thoughts
and feelings
respond with
an appropriate
emotion

13. Systemizing
Analysing or
building a system

14. sarcastic stern
suspicious dispirited
Females Males AS
22.1 19.5 16.6
JCPP
(2.0) (2.6) (2.9) 1997

15. Females > Males > Autism
Left Inferior Frontal Gyrus
fdfd

16. Females > Males >
Autism(EQ)
• People often tell me I went too far in driving my point
home in a discussion
• I often find it difficult to judge if something is rude or
polite
AS 20.4 (11.6)
Males 41.8 (11.2)
Females 47.2 (10.2)
JADD 2004

17. Females > Males > Autism
Corpus Planum
Callosum Temporale

18. Autism > Males > Females
Systemising Quotient
AS 35.9 (15.2)
Males 30.3 (11.7)
Females 24.1 (9.5)

19. Autism > Males > Females
AS Controls
16.3 10.3
(3.1) (2.8)

20. Autism > Males > Females
Females Males AS
66.7 46.2 32.2
(36.7) (20.5)
(27.0)
JCN, 1997

21. Females > Males > Autism
Posterior Parietal Cortex
l eF se >m Ma l ae ls e> s M a l e s C o n Ct ro on ltsr >o As >S C S C
l A
B a r o n - C o h e n e t a l., R in g e t a l., M a n ja ly e t a l.,
n - C o h e2 n0 0 e6 t , Ba lr . a, i n C o g n R i n g e t 1a 9l . 9, 9 , B r a i n M a n 2 j 0a l0y 7 ,e Nt ea lu . ,r o i m a g e Lee
6 , B r a in C o g n 1 9 9 9 , B r a in 2 0 0 7 , N e u r o im a g e N e

22. Autism > Males > Females
AS 35.8 6.5
AQ Males 17.8 6.8
Females15.4 5.7
BC et al, 2001

23. Autism > Males > Females
Schumann et al 2010 J Neurosci
Amygdala

26. Diff Men Women AS
E>S 17 44 1
S>E 54 17 27
S >> E 6 0 65
Int. J. Clin Neuropsych (2006)

27. % %

28. Pierce et al 2010
Arch Gen Psychiatry

31. Fetal sex steroids (androgens)
• fetal
testosterone
(FT)
• males
produce
double
• organizationa
l effects

32. Cambridge Amniocentesis Study
• 12-19 weeks in pregnancy (n = 619)
• 12, 24, 48, 96 months follow-up

33. Feeling sorry bored
interested joking
Empathy
Fetal Testosterone

34. Systemizing
Euro J Endocrin 2006

35. Attention
to
detail
Auyeung et al, 2012

36. 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.
Autistic traits
JADD, 2001;
Auyeung et al, 2009

37. Corpus
callosum
(Chura et al 2009)
3 0 .0
R>L
2 2 .5
1 5 .0
y
7 .5
m
A
e
y
r
s
t
0
m
V
h
o rF
a
r
H e-
I
- 7 .5
f
- 1 5 .0
r = 0 .5 8
L>R
r 2 = 0 .3 4
- 2 2 .5
- 0 .7 5 - 0 .5 0 - 0 .2 5 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0
F e ta l Te sto ste ro n e

38. Planum Temporale
Lombardo et al 2012
P o s it iv e C o r r e la t io n
N e g a t iv e C o r r e la t io n
p lO F C
R T P J /p S T S
P T /P O
P T /P O

39. Historic Birth Cohort Denmark
(n>100,000)
Singletons born 1993-99
(n=19,677)
Autism and Controls
AS (n=70) (n=219)

40. Cambridge-Denmark Study:
ASC (n = 59) Controls (n = 219)
progesterone
17α-hydroxy cortisol
progesterone
androstenedione
testosterone The Δ4-sex steroid pathway
CYP17-mediated
(Chakrabarti et al 2009)

41. 10 sex steroid genes
AS case-control EQ /AQ
HSD11B1
CYP11B1*
LHCGR HSD17B4
ESR1
CYP17A1 HSD17B2*
ESR2
CYP19A1
SCP2
(* = EQ only)
Chakrabarti et al, 2009 Autism Research

42. Hormonal factors
• Puberty
(Tordjeman et al, 1997; Ingudomnukul et al, 2007)
• Polycystic Ovary Syndrome (PCOS)
(Ingudomnukul et al, 2007; Kao et al, 2010)
• 2D:4D ratio
(Manning et al 2001; Swettenham et al, 2006; Noipayak,
2009)
• Salivary testosterone
(Schmidtova et al, 2010)
• Serum androstenedione

43. Conclusions / Future directions
• Fetal androgens/sex steroids play a role in
sexual dimorphism in brain development and
behaviour, especially autistic traits
• Fetal sex steroids interact with genetic factors
and postnatal experience
• The Cambridge-Denmark study is the strong
test of the fetal androgen theory of autism

44. www.autismresearchcentre.com
Thanks to
The Nancy Lurie Marks Foundation
Medical Research Council UK
Wellcome Trust UK
Target Autism Genome
NIHR CLAHRC

45. The steroidogenic pathway