For our next talk, in the Digital Phenotyping seminar series, we will hear from Prof Jason Lerch, Professor of Neuroscience and the Director of Preclinical Imaging, Wellcome Centre for Integrative Neuroimaging (WIN), University of Oxford; Adjunct Scientist, Mouse Imaging Centre (MICe) of the Hospital for Sick Children and Professor of Medical Biophysics, University of Toronto, on Wednesday20 November 2:00pm – 3:00pm, at the Big Data Institute (BDI).
Title: Integrating mouse and human imaging studies of autism to identify molecularly defined subtypes
Date: Wednesday 20 November 2024
Time: 2:00 pm – 3:00 pm
Venue: BDI/OxPop, Seminar Room 0; followed by refreshments in the atrium
Abstract: The high degree of heterogeneity in autism and related neurodevelopmental disorders (NDDs) presents a substantial hurdle for the accurate assessment of individuals and the development of effective therapies. This has led to the search for clusters of individuals sharing common biology and thus greater uniformity in prognosis or treatment response. With only approximately 20% of individuals presenting with an identified likely causative gene, clustering efforts thus far have focused on using clinical, cognitive, or brain imaging phenotypes. However, such data driven clusters in autism and related NDDs have not been linked to potentially actionable underlying mechanisms, limiting their utility. Here we show, using joint modelling of brain imaging data from 135 mouse models and 1,230 human individuals, that NDDs divide into broad groups with a diffuse set of underlying molecular pathways. Further subdivisions isolate three cross-species transdiagnostic subgroups with precise signalling associations: one showing a chromatin/transcription motif, another being synaptic in origin, with the third representing a mix of transcription, GPCR, and Notch signalling. The identified subgroups differentiate based on extent and direction of brain anatomy changes in areas of the cerebral cortex, cerebellum, corpus callosum, and midbrain. These groups are transdiagnostic and include participants with autism, ADHD, or OCD; therefore, a pure autism cluster is elusive. Our results demonstrate that autism and related NDDs subdivide into clusters with cohesive underlying biological mechanisms, opening the door to future stratified treatment trials when and if treatment is desired. This work provides further evidence that the diagnostic boundaries between autism and related NDDs do not clearly reflect underlying biology.
Short bio: Jason Lerch is Professor of Neuroscience and the Director of Preclinical Imaging at the Wellcome Centre for Integrative Neuroimaging (WIN) at the University of Oxford and an Adjunct Scientist at the Mouse Imaging Centre (MICe) of the Hospital for Sick Children and Professor of Medical Biophysics at the University of Toronto. Jason joined WIN in March of 2019; prior to that he completed his Ph.D. in 2005 in the Department of Neurology and Neurosurgery at McGill University and a post-doctoral fellowship at MICe from 2005-2008 with Dr. Mark Henkelman and Dr. John Sled. He received his B.A. in 1999 in Anthropology and Social Studies of Medicine from McGill University. His Ph.D. research, under the supervision of Dr. Alan Evans, was on in-vivo measurements of cortical thickness from MRI. His current research focus is on detecting neuroanatomical changes due to behavioural and genetic manipulations in tightly controlled mouse models, primarily related to neurodevelopmental disorders, and to relate these findings to sadly not so well controlled human subjects. As an antidote to these academic pursuits, he likes to leave the city and hike in the woods, whenever possible.
Hybrid Option:
Please note that these meetings are closed meetings and only open to members of the University of Oxford. Please respect our speakers and do not share the link with anyone outside of the University. The purpose of these seminars is to foster more communication among employees throughout the University, so we strongly advise in-person attendance whenever feasible.
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