This exciting opportunity, taking research from 'bench to bedside' is co-funded by the MRC, Autistica, and the Sackler Institute for Translational Neurodevelopment. It links to major international research networks, and other Sackler Centres in the UK and USA.The project focuses on Autism Spectrum Disorder (ASD) - a lifelong neurodevelopmental condition affecting over 1% of the population and costing the UK over £27 billion/year. ASD individuals are also at very high risk of suffering from additional mental health problems (e.g. depression and anxiety). Treatments for ASD are urgently needed, but have been hard to find - because its causal mechanisms are poorly understood, and there is no means to fractionate the aetiologically (and clinically) heterogeneous ASD population. However, there is fresh optimism based on evidence from our lab, and others, that individuals with ASD have a significant difference in the balance of excitatory glutamate (E) and inhibitory GABA (I), arising from: a) synapse dysfunction and/or b) microglial activation (neuroinflammation) There is also evidence that this abnormality is related to severity of clinical symptoms in ASD – including mental health comorbidities.This project, therefore, brings together clinical and preclinical laboratory approaches to address this question. The student will work on our fully translatable Magnetic Resonance Spectroscopy (MRS) and Positron emission tomography (PET) platform to examine glutamate/GABA flux, and markers of neuroinflammation, in adults with ASD and in relevant preclinical models. The aim is to delineate brain inflammatory abnormalities in ASD, determine how these relate to clinical symptoms (including common mental health co-morbidities) and interact with differences in glutamate/GABA, and to measure how brain glutamate/GABA in ASD responds to existing drugs which modulate microglia and have an established safety profile. This may lead to new:1. treatments for ASD targeting both core and associated symptoms. 2. tools to identify biologically homogeneous sub-groups within the spectrum. 3. methods to predicting who will or won’t respond to treatment.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
