{"id":29479,"date":"2026-05-29T16:23:32","date_gmt":"2026-05-29T14:23:32","guid":{"rendered":"https:\/\/opentalk.iit.it\/?p=29479"},"modified":"2026-05-29T16:25:47","modified_gmt":"2026-05-29T14:25:47","slug":"brain-scans-reveal-two-distinct-subtypes-of-autism-with-different-underlying-biology","status":"publish","type":"post","link":"https:\/\/opentalk.iit.it\/en\/brain-scans-reveal-two-distinct-subtypes-of-autism-with-different-underlying-biology\/","title":{"rendered":"Brain Scans Reveal Two Distinct Subtypes of Autism With Different Underlying Biology"},"content":{"rendered":"<p style=\"font-weight: 400;\"><em>The study has linked distinct patterns of brain connectivity in autism to different underlying molecular mechanisms, offering a biological foundation for precision medicine approaches<\/em><\/p>\n<p><!--more--><\/p>\n<p style=\"font-weight: 400;\">An international research team led by Istituto Italiano di Tecnologia (IIT Italian Institute of Technology) in Rovereto (Trento, Italy) and the Child Mind Institute in New York (USA), and in collaboration with researchers from the University of Trento, Italy, has shown that it is possible to identify at least two distinct subtypes of autism, defined by their patterns of brain connectivity. In the \u201chyperconnectivity\u201d subtype, brain areas communicate more than usual; in the \u201chypoconnectivity\u201d subtype, communication between brain areas is reduced. The study aims to develop tools for precise, personalized autism care and support. The research paper was published in the international journal <a href=\"https:\/\/doi.org\/10.1038\/s41593-026-02287-z.\">Nature Neuroscience<\/a>.<\/p>\n<p style=\"font-weight: 400;\">The research study was coordinated by Alessandro Gozzi, PhD, director of the Center for Neuroscience and Cognitive Systems (CNCS) at the IIT and Adriana Di Martino, MD, founding director of the Autism Center at the Child Mind Institute, and it represents the first systematic effort to decode human brain imaging patterns (via fMRI) by tracing them back to their molecular underpinnings in mouse models. By linking patterns of connectivity to specific biological pathways, the findings offer a foundation for precision medicine approaches.<\/p>\n<p style=\"font-weight: 400;\">Therefore, the researchers analyzed functional connectivity across 20 mouse models and brain scans from 940 children and young adults with autism and over 1,000 neurotypical individuals. The findings revealed two reproducible autism subtypes: one characterized by reduced brain connectivity (hypoconnectivity) linked to synaptic pathways, the other by increased connectivity (hyperconnectivity) associated with immune-related systems. Together, these subtypes accounted for approximately 25% of individuals with autism examined in the study.<\/p>\n<p style=\"font-weight: 400;\">&#8220;<em>For decades, we\u2019ve observed tremendous variability in how autism manifests, but we lacked direct evidence that these differences reflected distinct underlying biology,&#8221;<\/em> said<strong> Dr. Alessandro Gozzi, at Italian Institute of Technology. \u201c<\/strong><em>Our approach enabled us to isolate specific genetic and immune factors, then translate those signatures to human brain scans, showing that different connectivity patterns encode different mechanistic pathways underlying autism.\u201d<\/em><\/p>\n<p style=\"font-weight: 400;\">The team combined brain imaging with genetic and biochemical analyses in mouse models, linking connectivity patterns to specific alterations in cellular function. This revealed how specific molecular pathways, including synaptic and immune-related mechanisms, manifest as distinct connectivity patterns observable with fMRI. The study established biological reference patterns from mice that guided subtype identification in human brain scans.<\/p>\n<p style=\"font-weight: 400;\"><em>&#8220;The mouse models gave us a biological &#8216;Rosetta Stone,'&#8221; said <strong>Dr. Adriana Di Martino at the Child Mind Institute<\/strong>. &#8220;We could see which biological pathways drive which connectivity signatures, then search for those same patterns in humans.&#8221;<\/em><\/p>\n<p style=\"font-weight: 400;\">The human data came from the Autism Brain Imaging Data Exchange (ABIDE) \u2014 a pioneering neuroimaging initiative co-founded by Dr. Di Martino that aggregates datasets from research laboratories worldwide \u2014 and the Child Mind Institute.<\/p>\n<p style=\"font-weight: 400;\">The analyses identified corresponding hypo- and hyperconnectivity subtypes in the human data. Gene expression analyses confirmed that human brain regions showing hypoconnectivity were enriched for synaptic genes, while hyperconnected regions showed enrichment for immune-related genes \u2014 mirroring the mechanisms identified in mouse models. Importantly, the subtypes were reproducible across independent datasets, validating their biological consistency.<\/p>\n<p style=\"font-weight: 400;\"><em>&#8220;Finding the same subtypes reproducible across dozens of independent research sites was critical validation<strong>,&#8221; <\/strong>added<strong> Dr. Gozzi.<\/strong><\/em><\/p>\n<p style=\"font-weight: 400;\">The two subtypes exhibited different functional brain architecture and showed modest differences on standardized autism assessments, with the hyperconnectivity subtype scoring moderately higher on autism severity measures.<\/p>\n<p style=\"font-weight: 400;\"><strong><em>\u201cBrain-based biological markers reveal distinctions that current behavioral assessments don&#8217;t fully capture,&#8221;<\/em><\/strong><em>noted <strong>Dr.<\/strong> <strong>Di Martino<\/strong>.<\/em><\/p>\n<p style=\"font-weight: 400;\">The researchers emphasize that while the current findings capture two dominant patterns of brain connectivity in autism, the full diversity of the spectrum likely encompasses additional subtypes that larger datasets and refined analytical approaches may reveal.<\/p>\n<p style=\"font-weight: 400;\">The research was made possible by an international collaboration coordinated by the Italian Institute of Technology and the Child Mind Institute, with funding from the Simons Foundation Autism Research Initiative, the European Research Council through the #DISCONN and #BRAINAMICS projects, the Brain and Behavior Foundation, the Fondazione Telethon, and the US National Institute of Mental Health.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The study has linked distinct patterns of brain connectivity in autism to different underlying molecular mechanisms, offering a biological foundation for precision medicine approaches<\/p>\n","protected":false},"author":5,"featured_media":29483,"comment_status":"closed","ping_status":"closed","sticky":true,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5104,4552,5039,5080],"tags":[],"class_list":["post-29479","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-life-science-en","category-en-news","category-news-en","category-press-release-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - 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