Kavli Affiliate: Graeme Davis
| Authors: Jacob Ellegood, Antoine Beauchamp, Yohan Yee, Gabe Devenyi, Justine Ziolkowski, Lily Qiu, Rand Askalan, Muhammad Ayub, Philipp Suetterlin, Alex Donovan, M. Albert Basson, Katherine M Quesnel, Nathalie G Berube, Taeseon Woo, David Beversdorf, Hans Bjornsson, Randy Blakely, Froylan Calderon de Anda, Jacqueline Crawley, Jennifer Crosbie, Brian O Orr, Graeme W Davis, Matthew Genestine, Emanuel DiCicco-Bloom, Sean Egan, Kyle D Fink, Sarah Asbury, Jonathan Lai, Kelly Rilett, Jane A Foster, John B Vincent, Paul Frankland, Stelios Georgiades, Olga Penagarikano, Daniel Geschwind, Roman J Giger, Sander Markx, Joseph Gogos, Christelle Golzio, Rafaela Goveia, Alyson Muotri, Marco Pagani, Alessandro Gozzi, Laura K Pacey, David Hampson, Tzyy-Nan Huang, Tzu-Li Yen, Yi-Ping Hsueh, Alana Iaboni, Megha Amar, Lilia M Iakou cheva, Jessica K Jones, Elizabeth Kelly, Brigette Kieffer, Mihyun Bae, Hwajin Jung, Hyosang Kim, Haram Park, Junye Daniel Roh, Eunjoon Kim, Genevieve Konopka, Christine Laliberte, Julie L Lefebvre, Kathie Eagleson, Pat Levitt, Aurea Martins Bach, Thomas J Cunningham, Elizabeth Fisher, Karla Miller, Shoshana Spring, Alea Mills, Rob Nicolson, Leigh Spencer Noakes, Brian J Nieman, Cesar P Canales, Alex S Nord, Lauryl MJ Nutter, Elaine Tam, Lucy R. Osborne, Amy Clipperton-Allen, Damon Page, Brooke Babineau, Hyang Mi Moon, Theo D Palmer, Keqin Yan, David Picketts, Qiangqiang Xia, Craig M Powell, Armin Raznahan, Diane M Robins, Gavin Rumbaugh, Ameet S Sengar, Michael William SALTER, Russell James Schachar, Lia D’Abate, Clarissa A Bradley, Stephen W. Scherer, Nycole W. Copping, Stela P Petkova, Jill L Silverman, Karun Kar Singh, Nam-Shik Kim, Ki-Jun Kar Yoon, Guo-Li Ming, Hongjun Song, Jin Nakatani, Nobuhiro Nakai, J Nomura, Toru Takumi, Margot Taylor, Peter Tsai, Matthew Bruce, Ka ren L Jones, Judy Van de Water, Matthijs C Van Eede, Travis M Kerr, Christopher L Muller, Jeremy Veenstra VanderWeele, Marlee M Vandewouw, Rosanna Weksberg, Rachel Wevrick, Haim Belinson, Anthony Wynshaw-Boris, Konstantinos Zarbalis, Brett Trost, Rogier B Mars, Mallar Chakravarty, Azadek Kushki, Evdokia Anagnostou and Jason P Lerch
| Summary:
The heterogeneity of autism and related neurodevelopmental conditions has impeded accurate prognoses and treatment discovery. Using translational neuroimaging across 135 mouse models (3,515 mice) and two human MRI datasets (n = 1,234 and n = 1,015), we derived participant subgroups from shared neuroanatomical features. These subgroups did not distinguish autism, ADHD, or OCD diagnoses and only modestly differentiated cognitive and behavioural phenotypes. Instead, they mapped onto four molecular pathways: (1) synaptic function; (2) MAPK and Wnt signalling; (3) chromatin modification and cellular stress responses; and (4) broader chromatin, immune, and second-messenger signalling pathways. This framework bridges preclinical models and idiopathic human neurodevelopmental conditions, linking patients to biologically relevant molecular mechanisms.