Autistic traits, autism spectrum conditions, and foetal testosterone

Lead Research Organisation: University of Cambridge
Department Name: Psychiatry

Abstract

Autism spectrum conditions (ASC) affect males far more often than females. This is likely to reflect the influence of hormones, genetics, diagnostic practice, or all three factors. This program grant tests the first of these by following up children whose mothers had amniocentesis, and where the amniotic fluid tesosterone levels are measured. It tests in both a small British Biobank (linked to 500 children) and in the much larger Danish Biobank (linked to 90,000 children) if foetal testosterone levels are elevated in children who later show more autistic traits, or who go on to receive a diagnosis of autism or Asperger Syndrome. In addition, since amniocentesis samples may not be representative of the general population, we test if foetal testosterone is correlated with newborn testosterone levels measured in blood spots collected at birth, and in saliva at 3 months, since ultimately such tests are less invasive, have less risk, and could be taken from every baby. We also measure neonatal testosterone levels in children later diagnosed with autism. Finally, we test a rare medical condition (AIS) in which males cannot bind foetal testosterone, to test the prediction that such males should have fewer autistic traits than typical males. The range of planned studies will help answer the question as to whether foetal testosterone increases the risk of autistic traits and ASC.

Technical Summary

In our previous MRC program we tested if foetal testosterone (FT) has an effect on variation in behavioural development in children whose mothers had had amniocentesis. We found that FT was inversely correlated with frequency of eye contact at 12 months, vocabulary size at 18 and 24 months, peer relations, empathy, narrow interests, and number of autistic traits at 48 months. We also found that females with congenital adrenal hyperplasia (CAH) had more autistic traits than unaffected females. In this new proposal we wish to extend these studies in six ways: (1) We will repeat the earlier studies but expand the sample size from n = 70 to n = 500, in order to increase power; (2) We will add an independent measure of autistic traits (the AQ) to test if the relationship between FT and autistic traits is robust; (3) We will test FT levels in n = 467 cases of diagnosed autism vs. n = 934 controls, whose amniotic samples are in the Danish Biobank, to test categorical diagnosis of ASC in relation to FT; (4) We will test if FT levels in n = 500 children from amniotic fluid are correlated with neonatal tesosterone (NT) from Guthrie blood spots; (5) We will test NT in n = 100 cases of ASC from Guthrie blood spots, vs. 100 controls; and (6) We will test individuals with Androgen Insensitivity Syndrome (AIS), predicting they should have fewer autistic traits than chromosomally-matched controls. This design will test the validity of the foetal androgen theory of autistic traits and autism.

Publications

10 25 50

publication icon
Allison C (2007) The Childhood Asperger Syndrome Test (CAST): test-retest reliability in a high scoring sample. in Autism : the international journal of research and practice

 
Guideline Title Autism in Adults
Description Chair of NICE Guideline Update
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact Creation of a clinical pathway for adults with autism and Asperger Syndrome
 
Description Dept of Health Autism Strategy Program Board (member)
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Implementation of the Autism Strategy that came out of the Autism Act 2009.
 
Description Development of new screening and clinical instruments
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Many clinicians now use our questionnaires, such as the EQ, AQ, and CAST in their clinics
 
Description NICE Guideline Development Group for Adults with Autism (Chair)
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Baron-Cohen chaired the above group which published the NICE guideline in 2012.
 
Description Asperger Syndrome Project Grant
Amount £200,000 (GBP)
Organisation Baily Thomas Charitable Fund 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2007 
End 01/2012
 
Description Autistica
Amount £40,000 (GBP)
Organisation Autistica 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2017
 
Description CLAHRC
Amount £450,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR CLAHRC East of England
Sector Public
Country United Kingdom
Start 01/2009 
End 01/2012
 
Description Cambridge Asperger Syndrome Clinic Project Grant/Three Guineas Charitable Trust
Amount £300,000 (GBP)
Organisation Three Guineas Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2006 
End 01/2011
 
Description EU IMI
Amount £750,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2012 
End 04/2017
 
Description EU Inclusion
Amount £450,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2011 
End 01/2014
 
Description MRC AIMS Consortium
Amount £200,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2007 
End 01/2012
 
Description NIHR CLAHRC
Amount £45,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR CLAHRC East of England
Sector Public
Country United Kingdom
Start 04/2016 
End 07/2017
 
Description TWCF
Amount £1,800,000 (GBP)
Organisation The John Templeton Foundation 
Sector Academic/University
Country United States
Start 12/2015 
End 12/2018
 
Description Wellcome Project Grant (Foetal testosterone effects on brain development)
Amount £350,000 (GBP)
Funding ID 091774 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2010 
End 01/2013
 
Title Autism Research Centre (ARC) Research Volunteers Database 
Description This now contains 30,000 individuals who have registered to take part in our research. They are either families with an autistic relative, people with autism themselves, and 'control' volunteers. 
Type Of Material Biological samples 
Year Produced 2007 
Provided To Others? Yes  
Impact Publications 
 
Title Autism genetic biobank 
Description DNA from cases of autism and controls 
Type Of Material Biological samples 
Year Produced 2012 
Provided To Others? Yes  
Impact Publications 
 
Title Phenotyping questionnaires 
Description The Autism Spectrum Quotient (AQ) [child, adolescent, and adult versions]; the Empathy Quotient (EQ) and Systemizing Quotient [child, adolescent, and adult versions]; and the QCHAT (Quantitative Checklist for Autism in Toddlers). 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact Publications 
 
Title CARD: Cambridge Autism Research Database 
Description To recruit participants with autism into research and to share data with other researchers 
Type Of Material Database/Collection of data 
Year Produced 2008 
Provided To Others? Yes  
Impact Publications 
 
Description Asperger Genetics 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Collection of samples
Collaborator Contribution Genotyping
Impact Analysis underway
Start Year 2009
 
Description Autism Genetics 
Organisation Illumina Inc.
Department Illumina
Country United Kingdom 
Sector Private 
PI Contribution sample collection for genetic sequencing
Collaborator Contribution genetic sequencing
Impact none yet
Start Year 2016
 
Description Autism Genetics and Brain Scanning 
Organisation King's College London
Department MRC Social Genetic and Developmental Psychiatry Centre (SDGP)
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of studies, data collection, data analysis, drafting of papers
Collaborator Contribution Genotyping and MRI Imaging
Impact Publications
Start Year 2007
 
Description Autism Imaging 
Organisation King's College London
Department MRC Social Genetic and Developmental Psychiatry Centre (SDGP)
Country United Kingdom 
Sector Academic/University 
PI Contribution MRC AIMS (Autism Imaging Multicentre Study) leveraging EU-AIMS (Autism Interventions Multicentre Study)
Collaborator Contribution Extending these studies to females on the autism spectrum
Impact Publications
Start Year 2011
 
Description Autism Imaging 
Organisation Medical Research Council (MRC)
Department MRC Cognition and Brain Sciences Unit
Country United Kingdom 
Sector Public 
PI Contribution Providing participants with autism and co-designing experiments
Collaborator Contribution Recruiting from the Autism Research Centre database
Impact Publications
Start Year 2010
 
Description Autism Stem Cell 
Organisation National University of Singapore
Department Department of Chemistry
Country Singapore 
Sector Academic/University 
PI Contribution providing PhD student to work in lab
Collaborator Contribution training PhD student in stem cell research
Impact paper under review
Start Year 2014
 
Description BASIS 
Organisation Birkbeck, University of London
Department Department of Psychological Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of studies
Collaborator Contribution Design of studies and access to samples
Impact Publications
Start Year 2008
 
Description Danish BioBank 
Organisation The Statens Serum Institute (SSI)
Country Denmark 
Sector Public 
PI Contribution Design of studies
Collaborator Contribution Hormone assays, provision of samples, access to the Register
Impact Publications
Start Year 2007
 
Title Autism screening instruments 
Description Questionnaires for primary clinical practitioners 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2012
Licensed Yes
Impact Cambridge Enterprise has taken on the role of licensing the use of these questionnaires to companies who wish to use them and profits come back to autism research in Cambridge
 
Title Prenatal steroid hormones in amniotic fluid as biomarkers for autism 
Description Prenatal amniotic sex steroid hormones are elevated in autism 
IP Reference In UK only 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact None yet
 
Title Oxytocin nasal spray trial in autism 
Description MRC Program Grant 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact Paper submitted for publication 
 
Title The Transporters DVD 
Description This DVD helps young children with autism to recognize emotions. The research was funded by the DCMS and MRC staff contributed to it. After the research was completed the DCMS ran a tender for distribution of the DCMS and the authors of the DVD successfully won the tender. We set up a company to distribute the DVD internationally (Changing Media Development Litd) and a website (www.thetransporters.com) and the plan is to hand this to an autism research charity so that revenue goes back into research. 
Type Therapeutic Intervention - Psychological/Behavioural
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact Publication 
URL http://www.thetransporters.com
 
Description International Congress of Autism 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact International Congress of Autism
Year(s) Of Engagement Activity 2016
 
Description BBC Radio 4 Today Programme 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed on pre-natal screening for autism; male brains; and gender differences in STEM

Disseminating scientific findings to a wider audience, feedback via radio 4 website, entering a public debate on ethical and moral issues
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description Berlin School of Mind and Brain - 'The prenatal sex steroid theory of autism' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Berlin School of Mind and Brain - 'The prenatal sex steroid theory of autism'
Year(s) Of Engagement Activity 2016
 
Description Chair of Brain Canada 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact 6 awards made of approximately $5m each

Canadian autism research was expanded
Year(s) Of Engagement Activity 2013
 
Description Charles Simonyi Lecture - 'Autism and minds wired for science' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Charles Simonyi Lecture - 'Autism and minds wired for science'
Year(s) Of Engagement Activity 2016
 
Description Church and community conference organised by Diocese of Ely 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 70 people attended conference and particpated in question and answer session

Increased awareness of ASC and stimulated church policy
Year(s) Of Engagement Activity 2009
 
Description Conference and concert, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Conference open to general public and concert by individuals with autism spectrum conditions

allowed general public to mix with researchers and provided a forum for discussing research
Year(s) Of Engagement Activity 2007,2008,2014
 
Description Conference, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Reaching alumni and the general public to enable questions after the talk, book signing of popular science books, and to recruit people into research

Enabled public to find out more about research on autism
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description Dalai Lama Centre - 'Zero Degrees of Empathy' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Dalai Lama Centre - 'Zero Degrees of Empathy'
Year(s) Of Engagement Activity 2016
 
Description EMBL Speech - 'The prenatal sex steroid theory of autism' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Making scientific research accessible to European colleagues in many fields
Year(s) Of Engagement Activity 2016
 
Description Guardian Hay Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 50+ people attended the talk and particpated in a question and answer session

Increased awareness of ASC
Year(s) Of Engagement Activity 2010,2011,2012
 
Description Hans Albrecht Annual Memorial Lecture - 'Is autism a disorder?' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Hans Albrecht Annual Memorial Lecture - 'Is autism a disorder?'
Year(s) Of Engagement Activity 2016
 
Description HowTheLightGetsIn 2016 - Debate 'Dancing with the Devil'; Debate 'Doing Right and Feeling Good' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact HowTheLightGetsIn 2016 - Debate 'Dancing with the Devil'; Debate 'Doing Right and Feeling Good'
Year(s) Of Engagement Activity 2016
 
Description Local College, School, and Charity Talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Baron-Cohen gives approximately one invited lecture per week to local schools, college, charities, community groups, clinicians, educators, or the press.

Our lab website now enables audiences to email in with queries about either research or where to get help for their family etc., and they receive a personal reply from one of our administrators. They also receive an annual Newsletter.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Open Meeting, Umbrella Autism Charity, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact 30 people attended and question and answer session afterwards

people enquired about participating in reserach
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Presentation to Cambridge Police Force 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Police officers received an autism alert card to help recognise people with ASC

Police awareness of ASC increased
Year(s) Of Engagement Activity 2009
 
Description Press releases 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Press release via the journals (Brain, and Molecular Autism)

multiple media reports
Year(s) Of Engagement Activity 2013
 
Description Public Forum, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 100 people attended public forum, "Gendered Behaviour: what can science tell us?", organised by The Guardian/Cambridge University Press. Prof Baron-Cohen spoke and answered questions from the floor

Public debate on The Guardian website
Year(s) Of Engagement Activity 2010
 
Description Public Lecture, University of Reading 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 100 people attended including school teachers

Increased awareness of ASC
Year(s) Of Engagement Activity 2010
 
Description Public Lectures and Interviews and Media Articles 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Various articles and interviews in the media Prof Baron-Cohen generating public debate and dissemination of research to the general public

Encourages people diagnosed with autism and their families to add their details to database for research participants; enquiries and questions from the general public about research resulting from outreach activities
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description School Visit, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Prof Baron-Cohen talk to science society at a number of schools and 6th form colleges in Cambridge

Pupils approached centre asking for work experience, interested in studying psychology at university
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description Sixth form conference, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Prof Baron-Cohen lecture "Sex Differences in Mind" to AS/A2 sixth form students and answered questions on subject

enquiries from students about coming to ARC for work experience
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Sluckin Lecture 2016 - 'The prenatal sex steroid theory of autism' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Sluckin Lecture 2016 - 'The prenatal sex steroid theory of autism'
Year(s) Of Engagement Activity 2016
 
Description The Helmholz Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 200 students attended and discussed research

New collaborations with my host Prof Jack Van Honk
Year(s) Of Engagement Activity 2013
 
Description UN Speech 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Autism Awareness Day Key Note Speech
Year(s) Of Engagement Activity 2017
 
Description University of Oxford Cortex Club - 'The prenatal sex steroid theory of autism' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact University of Oxford Cortex Club - 'The prenatal sex steroid theory of autism'
Year(s) Of Engagement Activity 2016