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.
Organisations
- University of Cambridge, United Kingdom (Lead Research Organisation)
- The Statens Serum Institute (SSI) (Collaboration)
- National University of Singapore, Singapore (Collaboration)
- The Wellcome Trust Sanger Institute (Collaboration)
- Birkbeck, University of London (Collaboration)
- Medical Research Council (Collaboration)
- Illumina Inc. (Collaboration)
- King's College London, United Kingdom (Collaboration)
Publications
Adhya D
(2018)
Understanding the role of steroids in typical and atypical brain development: Advantages of using a "brain in a dish" approach.
in Journal of neuroendocrinology
Allison C
(2008)
The Q-CHAT (Quantitative CHecklist for Autism in Toddlers): a normally distributed quantitative measure of autistic traits at 18-24 months of age: preliminary report.
in Journal of autism and developmental disorders
Allison C
(2012)
Toward brief "Red Flags" for autism screening: The Short Autism Spectrum Quotient and the Short Quantitative Checklist for Autism in toddlers in 1,000 cases and 3,000 controls [corrected].
in Journal of the American Academy of Child and Adolescent Psychiatry
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
Andrews DS
(2017)
In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder.
in Cerebral cortex (New York, N.Y. : 1991)
Ashwin C
(2017)
Differences in change blindness to real-life scenes in adults with autism spectrum conditions.
in PloS one
Ashwin C
(2015)
Atypical integration of social cues for orienting to gaze direction in adults with autism.
in Molecular autism
Ashwin C
(2007)
Differential activation of the amygdala and the 'social brain' during fearful face-processing in Asperger Syndrome.
in Neuropsychologia
Ashwin C
(2009)
Positive and negative gaze perception in autism spectrum conditions.
in Social neuroscience
Ashwin E
(2009)
Eagle-eyed visual acuity: an experimental investigation of enhanced perception in autism.
in Biological psychiatry
| 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 |