A population-based twin-study of autism spectrum disorders: genetic and environmental sources of cognitive and clinical

Lead Research Organisation: King's College London
Department Name: Social Genetic and Dev Psychiatry Centre

Abstract

Autism is a devastating disorder affecting the ability to make social relationships, communicate and break out of rigid routines. Autism and autism spectrum disorders (ASD) affect over 500,000 families in the UK. While ASD is known to be heritable, the exact genes involved are not known. Similarly, despite much public concern, no environmental risk factors have been discovered. We aim to establish the largest twin study of ASD to date, within an existing study of all twins born in England and Wales in 1994-1996. We would assess twins with state-of-the-art diagnostic tools, and give tests for psychological strengths and weaknesses, as well as asking parents about possible environmental factors. Comparing identical and fraternal twins, and looking at the relationships between diagnosis, symptoms, and psychological and environmental measures, will identify possible subgroups within the autism spectrum. This work should speed the identification of genetic and environmental factors that, perhaps in interaction, predispose a child to autism. Discovering these factors is the first step in providing intervention and treatment for autism spectrum disorders.

Technical Summary

Progress in understanding the causes of and possible treatments for autism has been hampered by the heterogeneous nature of autism spectrum disorders (ASD). Autism is among the most heritable of psychiatric disorders, yet little progress has been made identifying genes, perhaps due to genetic heterogeneity within ASD. At the same time, lack of perfect concordance, plus a perception of rise in prevalence of ASD, has raised concern regarding possible environmental risk factors. We aim to investigate genetic and environmental sources of heterogeneity within ASD. The proposed project would establish the largest population-based twin sample of the full autism spectrum, with contemporaneous prospective developmental data, within a large normative sample. We propose to assess up to 200 ASD twin pairs and 100 comparison pairs (including IQ-matched controls) using gold-standard diagnostic assessments, a comprehensive cognitive battery, and targeted questions about putative environmental risk factors. With more than twice the sample size in existing published twin studies of ASD, we will have power to investigate; a) genetic subtypes/familial aspects of the phenotype for directed linkage and association studies; b) independence/unity of different symptom/cognitive domains within ASD; c) candidate environmental factors in relation to genetic vulnerability.

Publications

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Bolton PF (2009) Medical conditions in autism spectrum disorders. in Journal of neurodevelopmental disorders

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Bolton PF (2011) Epilepsy in autism: features and correlates. in The British journal of psychiatry : the journal of mental science

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Brunsdon VE (2014) Exploring the 'fractionation' of autism at the cognitive level. in Autism : the international journal of research and practice

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Carter Leno V (2019) Exploring the neurocognitive correlates of challenging behaviours in young people with autism spectrum disorder. in Autism : the international journal of research and practice

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Charman T (2011) Defining the cognitive phenotype of autism. in Brain research

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Curran S (2011) No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

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Curran S (2011) No major effect of twinning on autistic traits. in Autism research : official journal of the International Society for Autism Research

 
Description Contribution to policy document for NAS 'Getting on: growing older with autism'
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL http://www.autism.org.uk/gettingon
 
Description DSM-5 Autism Spectrum Disorder text - Happe
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Responsible for drafting text for new ASD criteria. Reflect impact of our research, e.g. severity ratings will be made separately for social and nonsocial festures of ASD, as a result of our research on the 'fractionable triad'.
 
Description DSM-V Workgroup on Neurodevelopmental Disorders: invited member of this workgroup devising diagnostic criteria for autism and related disorders; one of only two Europeans among the 12 workgroup members.
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact This workgroup is reponsible for devising, drafting and assessing the new criteria for autism and related disorders in the APA's DSM-V, to be published in 2012/13. DSM-V will have a major impact on clinical care and research practice.
 
Description Invited member of NAS Advisory Committee on Autism in Maturity
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description Parliamentary Commission presentation (Autism and ageing, 11th March, 2013)
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description President, International Society for Autism Research
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
URL http://www.autismspeaks.org/science/science-news/autism-researchers-without-borders
 
Description Baily Thomas Charitable Fund Project Grants
Amount £59,629 (GBP)
Organisation Baily Thomas Charitable Fund 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2012 
End 06/2014
 
Description EC FP7 funding (Psych CNVs project, PB)
Amount £428,000 (GBP)
Funding ID 223423 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start  
 
Description Gender Differences in Autism Spectrum Disorders in a Population-Based Twin Sample: testing three hypotheses for male preponderance.(Francesca Happe Emma Colvert)
Amount £540,514 (GBP)
Funding ID ES/M011488/1 
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 01/2016 
End 12/2018
 
Description NIHR Programme grant
Amount £2,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start  
 
Description Collaboration with Marco Battaglia 
Organisation San Raffaele Hospital
Department San Raffaele Scientific Institute (SRSI)
Country Italy 
Sector Academic/University 
PI Contribution Contributed conceptual and analytic expertise, to collaborate on novel analysis of relevant twin data from an Italian population sample.
Collaborator Contribution Collaborated on a recent paper exploring the phenotypic and genetic association between clumsiness and autistic-like traits. Pooled expertise in twin-modelling and theoretical perspectives, with this Italian team, bringing new twin data to bear on questions of shared interest
Impact Published paper: Moruzzi S, Ogliari A, Ronald A, Happ? F, Battaglia M. The nature of covariation between autistic traits and clumsiness: a twin study in a general population sample. J Autism Dev Disord. 2011 Dec;41(12):1665-74. PubMed PMID: 21347613.
Start Year 2009
 
Description 2013 Annual WiSETI (Women in Science, Engineering and Technology Initiative) Lecture, University of Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact More than 200 members of the public attended the lecture, which raised awareness and sparked questions about autism, social cognition and women in science.

Networking and further discussion with teachers and pupils.
Year(s) Of Engagement Activity 2013
 
Description 2014 Joint British Academy - British Psychological Society Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Over 150 members of the public attended a free, open evening lecture on MRC-funded research on typical and atypical social development (including autism). Audience included teachers from special schools and A-level Psychology students.

Discussion after the talk led to new connections, and increased interest in research. For example, a member of the audience visiting from an NGO in Pakistan asked about current research at IoP, and I arranged for her to visit and observe fMRI scanning sessions at the Centre for Neuroimaging Sciences at IoP.
Year(s) Of Engagement Activity 2014
URL http://www.britac.ac.uk/events/2014/Mind-Reading_as_a_gatekeeper.cfm
 
Description 8th International Congress Autism Europe 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited keynote for audience of teachers, parents, clinicians and researchers interested in autism.

Raised awareness.
Year(s) Of Engagement Activity 2007
 
Description APA meeting DSM-5 talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Presentation in a symposium on changes to diagnostic criteria for neurodevelopmental disorders in DSM-5, on the occasion of the publication of DSM-5 (as a workgroup member). Annual meeting of the American Psychiatric Association, San Francisco, May 21st 2013.

Contact with psychiatrists, discussion of practical implications of DSM-5 changes, communication and clarification of impact of our research.
Year(s) Of Engagement Activity 2013
 
Description Autism Summit organised by Italian Embassy in London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Presentation and round table on current research for a mixed audience.

Improved collaborative links with Italian health professionals and those interested in research and intervention for autism.
Year(s) Of Engagement Activity 2010
 
Description Autism and Developmental Disorders Colloquium Series, MIT and Autism Consortium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Invited to give a talk in the 'Autism and Developmental Disorders Colloquium Series', MIT and Autism Consortium, for students, clinicians and researchers.

Led to planned collaboration with researchers in MIT media labs interested in computer training of e.g. emotion recognition in autism.
Year(s) Of Engagement Activity 2007
 
Description Autistica Board meeting presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Invited presentation for the Board of the autism research charity Autistica, at their AGM.
Year(s) Of Engagement Activity 2018
 
Description British Academy meeting on Ethical Issues and Autism 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A British Academy one-day conference, held at the Royal Society, on 'Autism, Ethics and the Good Life', co-convened by F.Happe. This event was free to the public and promoted discussion of the ethical implications of, among other things, recent research on autism.

This event provoked discussion and established new connections between diverse groups, as well as involving families, individuals with ASD themselves and relevant self-advocacy groups.
Year(s) Of Engagement Activity 2012
 
Description Conference in Aalborg, Denmark 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Presented 'fractionated triad' hypothesis and relevant recent research to an audience of clinicians and related professionals.

Raised awareness of latest autism research, new views of autism, established possible future collaborations.
Year(s) Of Engagement Activity 2010
 
Description Designing Environments for Autism conference, Solihull 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Headteachers, architects and planners in education authorities attended this talk, explaining the relevance of our research on cognitive profiles in autism for the design of autism-friendly learning environments. This established contacts with educational experts, raised awareness of MRC-funded science and demonstrated the translational value of our studies.

Established contact with designers and educationalists for future discussion and collaboration.
Year(s) Of Engagement Activity 2010
 
Description Glebe School talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Established a school-research group partnership.
Year(s) Of Engagement Activity 2011
 
Description Hannah Devlin interview for Guardian re women and autism 
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 Media (as a channel to the public)
Results and Impact Gave an interview about under-diagnosis of women with autism, and our ESRC-funded research on gender and autism, to Hannah Devlin, who published a substantial piece in the Saturday Guardian and online. Piece was picked up by a range of other media outlets, and there was interest on social media, and a number of enquiries to our team.
Year(s) Of Engagement Activity 2018
URL https://www.theguardian.com/society/2018/sep/14/thousands-of-autistic-girls-and-women-going-undiagno...
 
Description Inaugural conference for founding of National Forum for Neuroscience and Special Education 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Over 100 educationalists attended the day, designed to increase communication between teachers working with special educational groups and scientists.

New collaborative links formed between special schools and neuroscience labs.
Year(s) Of Engagement Activity 2012
 
Description Invited Keynote address APAC 2009 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Gave keynote address and a second plenary session explaining our research to an Australian and pan-Asian audience of teachers, carers, clinicians and therapists working with children and adults with autism.

Discussion and possible future collaboration. Coverage in the media raising awareness of scientific issues.
Year(s) Of Engagement Activity 2009
 
Description Invited talk at stakeholder meeting, Amsterdam 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at pre-(INSAR)conference event for autism community stakeholders in Amsterdam.
Year(s) Of Engagement Activity 2018
URL https://www.nederlandsautismeregister.nl/nieuws/nieuwscontainer.html/2018/03/06/uitnodiging-insar-co...
 
Description Joint Royal Society/BA Discussion Meeting 'Talent & Autism' 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Organised and presented at a 2 day public Discussion Meeting on 'Talent and Autism' for researchers, parents, clinicians and interested lay audience.

Publication of special issue of the Philosophical Transactions of the Royal Society, and a book (OUP). Media coverage in press and on radio.
Year(s) Of Engagement Activity 2008
 
Description Keynote address IMFAR 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Invited Keynote address opening the International Meeting for Autism Research in London, with international audience of researchers, clinicians, and students interested in autism.

This talk recieved press and radio coverage.
Year(s) Of Engagement Activity 2008
 
Description Keynote at Autism Europe International Congress, Budapest 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Keynote presentation to audience of parents, carers, teachers ad clinicians interested in autism spectrum conditions, at 10th Autism-Europe International Congress, Budapest September 2013

New collaborative discussions and outreach to parents' associations and scientists in under-served areas of the world (e.g. Ukraine).
Year(s) Of Engagement Activity 2013
URL http://www.autismcongress2013.eu/index.php?lang=en
 
Description Keynote at British Neuropsychological Society meeting, November 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited keynote talk, led to discussion and potential collaboration with clinicians and academics.
Year(s) Of Engagement Activity 2017
 
Description Keynote talks for opening of Karolinska Institute centre for neurodevelopmental disorders 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Gave two invited addresses for the formal opening of the KIND (centre for neurodevelopmental disorders at the Karolinska Institute, Stockholm), to an audience of parents, policy makers, politicians, etc.

Raised awareness of the need for research on autism, the challenges faced by parents and individuals with these conditions, the implications of our recent findings.
Year(s) Of Engagement Activity 2010
 
Description King's Rosalind Franklin Lecture 2014 at Hay Literary Festival. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Around 200 members of the public attended a lecture about 'Talent and Autism', reporting MRC-funded research and stimulating a reconsideration of assets in individuals with autism spectrum disorder.

A large number of people from the audience asked for further information about our research.
Year(s) Of Engagement Activity 2014
URL https://www.hayfestival.com/p-8369-francesca-happe.aspx
 
Description Kingswood Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Evening lecture for general public, encouraged engagement in autism research and raised public awareness.
Year(s) Of Engagement Activity 2011
 
Description Lab visit to special school 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit to a special school with autism provision, along with a number of students, research officers and post-docs, to establish school-research group partnership.

Set in place school-research group partnership for exchange of ideas and information, to encourage translational aspects of our research.
Year(s) Of Engagement Activity 2010
 
Description MIT invited colloquium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited to speak in the Simons Center Colloquium Series, at the Simons Center for the Social Brain at MIT.
Year(s) Of Engagement Activity 2016
URL http://scsb.mit.edu/event/scsb-colloquium-series-francesca-happe-ph-d/
 
Description MRC Autism Forward Look and Review 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Invited presentation at MRC event for mixed audience, reviewing current MRC-funded autism research. Presented our on-going autism twin study and findings to date.

Established contact with special school headteacher interested in supporting autism research. This began an on-going reciprocal relationship (myself and research team giving talks for staff, and our students spending placements in the school).
Year(s) Of Engagement Activity 2009
 
Description Media showcase at ITV 
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 Media (as a channel to the public)
Results and Impact One of c. 15 female scientists invited to visit ITV for a media showcase with the Academy of Medical Sciences. Spoke about our autism gender work with follow-ups from journalists interested in covering findings in due course.
Year(s) Of Engagement Activity 2018
 
Description NAS 50th Anniversary Professionals Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Several hundred professionals working with individuals with ASD were brought up to date on recent research, including data and theoretical developments from our MRC-funded twin studies.

Follow-up interest in our work from clinicians, teachers and researchers.
Year(s) Of Engagement Activity 2012
 
Description NAS PDA video 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Podcast video interview about PDA, on NAS website, resulted in many people contacting our research group for more information.

Disseminated research information and gained volunteers for our ongoing studies.
Year(s) Of Engagement Activity 2011
 
Description National Autistic Society conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Over 300 teachers, parents and other profesionals attended an NAS conference on PDA. Many completed questionnaire measures for our research. School contacts were made. We received and answered questions via email or post from many concerned parents/teachers.

School contacts were made. We received and answered questions via email or post from many concerned parents/teachers.
Year(s) Of Engagement Activity 2011
 
Description Plenary at Annual Conference of General Adult faculty of Royal College of Psychiatrists 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave invited plenary talk at Annual Conference of General Adult faculty of Royal College of Psychiatrists. Good feedback, and particularly re changes in autism concept and research. Possible future collaborations with clinicians explored.
Year(s) Of Engagement Activity 2018
 
Description Presentation at Professionals Day for opening of new autism school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Teachers and members of LEAs heard about our latest research, with a lively question and answer session.

Established school-research links for discussion of what teachers would like to see further researched.
Year(s) Of Engagement Activity 2010
 
Description Prime Minister's Council for Science and technology scoping workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Invited to participate in PM Council for Science and technology scoping workshop on learning disability/neurodiversity and technology.
Year(s) Of Engagement Activity 2018
 
Description Royal Society Rosalind Franklin Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Over 150 people attended this free public lecture, which is also available to view on Royal Society TV, raising awareness of autism and research in this area.

Raised public awareness and interest.
Year(s) Of Engagement Activity 2011
 
Description Royal Swedish Academy of Sciences 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited talk and panel participation in symposium at the Royal Swedish Academy of Sciences, on the occasion of the the Swedish national committee for psychological sciences' Young Investigator Award. Stockholm, October 21st 2013.

New connections and potential collaborations with colleagues in Europe.
Year(s) Of Engagement Activity 2013
URL http://www.kva.se/en/Events-List/2013/Social-cognition-and-autism-/
 
Description SFARI workshop on sex differences in autism 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Simons Foundation Autism Research Initiative (SFARI) workshop to explore sex differences in autism. Invited presentation to small invited group of workshop participants. New York, October 8th, 2013.

Discussion with potential collaborators, and advising Simons Foundation on future funding priorities.
Year(s) Of Engagement Activity 2013
 
Description School visit and presentation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Presented our ongoing research and introduced talks by two MRC-funded PhD students working on the autism twin project, at Queensmill school for children with autism.

Ongoing dialogue with Headteacher about types of research staff would like to see undertaken; placement of our students in school for variable periods of hands-on experience.
Year(s) Of Engagement Activity 2009
 
Description Talk for National Autistic Society conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited to speak at a National Autistic Society conference in Leeds, for professionals (clinicians, teachers, therapists, etc), family members and other stakeholders.
Year(s) Of Engagement Activity 2019
 
Description Talk to Royal College of Physicians, Occupational Physicians Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Delivered, at the request of the RCP and Transport for London, a talk to raise understanding of autism and Asperger syndrome among Occupational Physicians, with particular emphasis on impact on employment.

Very good feedback, with inquiries for further information about our research from a number of attendees.
Year(s) Of Engagement Activity 2012