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(MRC DTP) Early development of Understanding the neurobiology of autism spectrum disorder in neurofibromatosis type 1

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  • Full or part time
    Prof J Green
    Prof A Theakston
    Dr S Garg
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Autism Spectrum Disorder (ASD) is a highly heritable neurodevelopmental disorder, with an onset around 3 years and population prevalence of >1%. It involves enduring impairments on social functioning and communication. Studies of the prodromal period leading to ASD in the first 3 years have already given key insights into the underlying developmental pathology of the disorder, but have been limited by use of heterogeneous samples of infants at high risk of polygenic familial autism.1 A complimentary more specific strategy is to study infants at risk due to monogenic syndromes in which the developmental biology is well known from animal models. Neurofibromatosis Type 1 (NF1) is an excellent monogenic disorder of this kind, which we and other groups have previously shown expresses ASD in nearly 45% of young affected children.2 With its internationally recognised NF1, communication and autism research centres, Manchester is already world-leading in this theme of work.
This project will advance understanding of early autism and communication development within our novel EDEN study (Early DEvelopment in NF1; co-PIs Green, Garg, Jones), which studies infants with NF1 prospectively at 5, 10 and 14 months of age using a battery of experimental measures. The DTP project will follow the 30 children from the EDEN cohort at 36 and 48 months of age, building on the previous prospective work and including ascertainment of the key endpoint ASD, ADHD and communication disorder outcomes. We will use eye-tracking, neurocognitive, EEG, language and behavioural measures to investigate and extend knowledge on known intermediate neural development biomarkers of these disorder trajectories. This data will then be compared to that from previous studies in the British Autism Study of Infant Siblings, on infants at risk of familial ASD (n=100) and low risk community samples (n=30); allowing us to test whether the NF1 cohort share the risk biomarkers that have been shown to be associated with ASD development in familial high risk groups.3-5 Such markers will then be used to predict risk for ASD and ADHD in NF1, for clinical stratification and to define intervention targets in treatment trials. Further insights gained from studying NF1 can be applied to common autism to develop new treatment strategies.

http://research.bmh.manchester.ac.uk/socialdevelopment/
http://www.lucid.ac.uk

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Szatmari, P., Chawarska, K., Dawson, G., Georgiades, S., Landa, R., Lord, C., . . . Halladay, A. (2016). Prospective Longitudinal Studies of Infant Siblings of Children With Autism: Lessons Learned and Future Directions. J Am Acad Child Adolesc Psychiatry, 55(3), 179-187.

2. Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans G et al. Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics. 2013 Dec;132(6):e1642-e1648.

3. Wan MW, Green J, Elsabbagh M, Johnson M, Charman T, Plummer F. Quality of interaction between at-risk infants and caregiver at 12-15 months is associated with 3-year autism outcome. Journal of Child Psychology and Psychiatry. 2013 Jul;54(7):763-771.

4. Orekhova EV, Elsabbagh M, Jones EJ, Dawson G, Charman T et al. EEG hyper-connectivity in high-risk infants is associated with later autism. Journal of Neurodevelopmental disorders. 2014;6(1).

5. Elsabbagh, M., Fernandes, J., Webb, S.J., Dawson, G., Charman, T., Johnson, M.H. and the BASIS Team. (2013) Disengagement of Visual Attention in Infancy Is Associated with Emerging Autism in Toddlerhood. Biological Psychiatry, 74(3), 189-194.



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