{"id":20142,"date":"2025-08-17T14:47:36","date_gmt":"2025-08-17T12:47:36","guid":{"rendered":"https:\/\/thesmartcityjournal.cibeles.net\/sin-categoria\/major-autism-study-uncovers-biologically-distinct-subtypes-paving-the-way-for-precision-diagnosis-and-care\/"},"modified":"2025-08-17T14:49:41","modified_gmt":"2025-08-17T12:49:41","slug":"major-autism-study-uncovers-biologically-distinct-subtypes-paving-the-way-for-precision-diagnosis-and-care","status":"publish","type":"post","link":"https:\/\/www.thesmartcityjournal.com\/en\/investigation\/major-autism-study-uncovers-biologically-distinct-subtypes-paving-the-way-for-precision-diagnosis-and-care","title":{"rendered":"Major autism study uncovers biologically distinct subtypes, paving the way for precision diagnosis and care"},"content":{"rendered":"<p><i><span style=\"font-weight: 400\">Researchers at Princeton University and the Simons Foundation have identified four clinically and biologically distinct subtypes of autism, marking a transformative step in understanding the condition\u2019s genetic underpinnings and potential for personalized care<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">Analyzing data from over 5,000 children in\u00a0<\/span><a href=\"https:\/\/sparkforautism.org\/portal\/page\/about-spark\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">SPARK<\/span><\/a><span style=\"font-weight: 400\">, an autism cohort study funded by the Simons Foundation, the researchers used a computational model to group individuals based on their combinations of traits. The team used a \u201cperson-centered\u201d approach that considered a broad range of over 230 traits in each individual, from social interactions to repetitive behaviors to developmental milestones, rather than searching for genetic links to single traits.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">This approach enabled the discovery of clinically relevant autism subtypes, which the researchers linked to distinct genetic profiles and developmental trajectories, offering new insights into the biology underlying autism. Their results were\u00a0<\/span><a href=\"https:\/\/www.nature.com\/articles\/s41588-025-02224-z\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">published<\/span><\/a><span style=\"font-weight: 400\">\u00a0July 9 in Nature Genetics.<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cUnderstanding the genetics of autism is essential for revealing the biological mechanisms that contribute to the condition, enabling earlier and more accurate diagnosis, and guiding personalized care,\u201d said senior study author\u00a0<\/span><a href=\"https:\/\/engineering.princeton.edu\/faculty\/olga-troyanskaya\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Olga Troyanskaya<\/span><\/a><span style=\"font-weight: 400\">, director of\u00a0<\/span><a href=\"https:\/\/pph.princeton.edu\/\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Princeton Precision Health<\/span><\/a><span style=\"font-weight: 400\">, the Maduraperuma\/Khot Professor of\u00a0<\/span><a href=\"https:\/\/www.cs.princeton.edu\/\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Computer Science<\/span><\/a><span style=\"font-weight: 400\">\u00a0and the\u00a0<\/span><a href=\"https:\/\/lsi.princeton.edu\/\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Lewis-Sigler Institute for Integrative Genomics<\/span><\/a><span style=\"font-weight: 400\">\u00a0at Princeton, and deputy director for genomics at the\u00a0<\/span><a href=\"https:\/\/www.simonsfoundation.org\/flatiron\/center-for-computational-biology\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Center for Computational Biology<\/span><\/a><span style=\"font-weight: 400\">\u00a0of the Simons Foundation\u2019s Flatiron Institute.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The study defines four subtypes of autism \u2014 Social and Behavioral Challenges, Mixed ASD with Developmental Delay, Moderate Challenges, and Broadly Affected. Each subtype exhibits distinct developmental, medical, behavioral and psychiatric traits, and importantly, different patterns of genetic variation.\u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Individuals in the\u00a0<\/span><b>Social and Behavioral Challenges<\/b><span style=\"font-weight: 400\">\u00a0group show core autism traits, including social challenges and repetitive behaviors, but generally reach developmental milestones at a pace similar to children without autism.\u00a0 They also often experience co-occurring conditions like ADHD, anxiety, depression or obsessive-compulsive disorder alongside autism. One of the larger groups, this constitutes around 37% of the participants in the study.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">The\u00a0<\/span><b>Mixed ASD with Developmental Delay<\/b><span style=\"font-weight: 400\">\u00a0group tends to reach developmental milestones, such as walking and talking, later than children without autism, but usually does not show signs of anxiety, depression or disruptive behaviors. \u201cMixed\u201d refers to differences within this group with respect to repetitive behaviors and social challenges. This group represents approximately 19% of the participants.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Individuals with\u00a0<\/span><b>Moderate Challenges<\/b><span style=\"font-weight: 400\">\u00a0show core autism-related behaviors, but less strongly than those in the other groups, and usually reach developmental milestones on a similar track to those without autism. They generally do not experience co-occurring psychiatric conditions. Roughly 34% of participants fall into this category.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">The\u00a0<\/span><b>Broadly Affected<\/b><span style=\"font-weight: 400\">\u00a0group faces more extreme and wide-ranging challenges, including developmental delays, social and communication difficulties, repetitive behaviors and co-occurring psychiatric conditions like anxiety, depression and mood dysregulation. This is the smallest group, accounting for around 10% of the participants.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">\u201cThese findings are powerful because the classes represent different clinical presentations and outcomes, and critically we were able to connect them to distinct underlying biology,\u201d said\u00a0<\/span><a href=\"https:\/\/lsi.princeton.edu\/people\/aviya-litman\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Aviya Litman<\/span><\/a><span style=\"font-weight: 400\">, a Ph.D. student at Princeton and co-lead author.\u00a0<\/span><\/p>\n<h2>Distinct genetics behind the subtypes<\/h2>\n<p><span style=\"font-weight: 400\">For decades, autism researchers and clinicians have been seeking robust definitions of autism subtypes to aid in diagnosis and care. Autism is known to be highly heritable, with many implicated genes.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cWhile genetic testing is already part of the standard of care for people diagnosed with autism, thus far, this testing reveals variants that explain the autism of only about 20% of patients,\u201d said study co-author\u00a0<\/span><a href=\"https:\/\/www.sfari.org\/people\/jennifer-foss-feig\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Jennifer Foss-Feig<\/span><\/a><span style=\"font-weight: 400\">, a clinical psychologist at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai and vice president and senior scientific officer at the\u00a0<\/span><a href=\"https:\/\/www.sfari.org\/\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Simons Foundation Autism Research Initiative<\/span><\/a><span style=\"font-weight: 400\">\u00a0(SFARI). This study takes an approach that differs from classic gene discovery efforts by identifying robust autism subtypes that are linked to distinct types of genetic mutations and affected biological pathways.<\/span><\/p>\n<p><span style=\"font-weight: 400\">For example, children in the Broadly Affected group showed the highest proportion of damaging\u00a0<\/span><i><span style=\"font-weight: 400\">de novo\u00a0<\/span><\/i><span style=\"font-weight: 400\">mutations \u2014 those not inherited from either parent \u2014 while only the Mixed ASD with Developmental Delay group was more likely to carry rare inherited genetic variants. While children in both of these subtypes share some important traits like developmental delays and intellectual disability, these genetic differences suggest distinct mechanisms behind superficially similar clinical presentations.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cThese findings point to specific hypotheses linking various pathways to different presentations of autism,\u201d said Litman, referring to differences in biology between children with different autism subtypes.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Moreover, the researchers identified divergent biological processes affected in each subtype. \u201cWhat we\u2019re seeing is not just one biological story of autism, but multiple distinct narratives,\u201d said\u00a0<\/span><a href=\"https:\/\/www.simonsfoundation.org\/people\/natalie-sauerwald\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">Natalie Sauerwald<\/span><\/a><span style=\"font-weight: 400\">, associate research scientist at the Flatiron Institute and co-lead author. \u201cThis helps explain why past genetic studies often fell short \u2014 it was like trying to solve a jigsaw puzzle without realizing we were actually looking at multiple different puzzles mixed together. We couldn\u2019t see the full picture, the genetic patterns, until we first separated individuals into subtypes.\u201d<\/span><\/p>\n<h2>Autism biology unfolds on different timelines<\/h2>\n<p><span style=\"font-weight: 400\">The team also found that autism subtypes differ in the timing of genetic disruptions\u2019 effects on brain development. Genes switch on and off at specific times, guiding different stages of development. While much of the genetic impact of autism was thought to occur before birth, in the Social and Behavioral Challenges subtype \u2014 which typically has substantial social and psychiatric challenges, no developmental delays, and a later diagnosis \u2014 mutations were found in genes that become active later in childhood. This suggests that, for these children, the biological mechanisms of autism may emerge after birth, aligning with their later clinical presentation.<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cBy integrating genetic and clinical data at scale, we can now begin to map the trajectory of autism from biological mechanisms to clinical presentation,\u201d said co-author Chandra Theesfeld, senior academic research manager at the Lewis-Sigler Institute and Princeton Precision Health.<\/span><\/p>\n<h2>A paradigm shift for autism research<\/h2>\n<p><span style=\"font-weight: 400\">This study builds on more than a decade of autism genomics research\u00a0<\/span><a href=\"https:\/\/engineering.princeton.edu\/news\/2019\/05\/28\/artificial-intelligence-detects-new-class-mutations-behind-autism\" target=\"_blank\" rel=\"nofollow noopener\"><span style=\"font-weight: 400\">led by Troyanskaya and collaborators<\/span><\/a><span style=\"font-weight: 400\">, supported by the Simons Foundation and the U.S. National Institutes of Health, and most recently by Princeton Precision Health, an interdisciplinary initiative launched in 2022. It is enabled by the close integration of interdisciplinary expertise in genomics, clinical psychology, molecular biology, computer science and modeling, and computational biology \u2014 with experts from Princeton Precision Health, the Flatiron Institute and SFARI.<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cThe Princeton Precision Health initiative uses artificial intelligence and computational modeling to integrate across biological and clinical data,\u201d said Jennifer Rexford, Princeton University provost and Gordon Y.S. Wu Professor in Engineering. \u201cThis initiative could not exist without the University\u2019s charitable endowment. Our investments allow experts to collaborate across a range of disciplines to conduct transformative research that improves human health, including the potential for major advances in the diagnosis and treatment of autism made possible in this exciting project.\u201d\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">\u201cIt\u2019s a whole new paradigm, to provide these groups as a starting point for investigating the genetics of autism,\u201d said Theesfeld. Instead of searching for a biological explanation that encompasses all individuals with autism, researchers can now investigate the distinct genetic and biological processes driving each subtype.<\/span><\/p>\n<p><span style=\"font-weight: 400\">This shift could reshape both autism research and clinical care \u2014 helping clinicians anticipate different trajectories in diagnosis, development and treatment. \u201cThe ability to define biologically meaningful autism subtypes is foundational to realizing the vision of precision medicine for neurodevelopmental conditions,\u201d said Sauerwald.<\/span><\/p>\n<p><span style=\"font-weight: 400\">While the current work defines four subtypes, \u201cthis doesn\u2019t mean there are only four classes,\u201d said Litman. \u201cIt means we now have a data-driven framework that shows there are at least four \u2014 and that they are meaningful in both the clinic and the genome.\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400\">Looking ahead<\/span><\/p>\n<p><span style=\"font-weight: 400\">For families navigating autism, knowing which subtype of autism their child has can offer new clarity, tailored care, support and community. \u201cUnderstanding genetic causes for more individuals with autism could lead to more targeted developmental monitoring, precision treatment, and tailored support and accommodations at school or work,\u201d said Foss-Feig. \u201cIt could tell families, when their children with autism are still young, something more about what symptoms they might \u2014 or might not \u2014 experience, what to look out for over the course of a lifespan, which treatments to pursue, and how to plan for their future.\u201d\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Beyond its contributions to understanding autism subtypes and their underlying biology, the study offers a powerful framework for characterizing other complex, heterogeneous conditions and finding clinically relevant disease subtypes. As Theesfeld put it: \u201cThis opens the door to countless new scientific and clinical discoveries.\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400\">Text: <\/span><span style=\"font-weight: 400\">Molly Sharlach, Office of Engineering Communications Stanford<\/span><\/p>\n<p><span style=\"font-weight: 400\">Image:\u00a0 Senior study author\u00a0Olga Troyanskaya (center) with Princeton researchers\u00a0Aviya Litman (left) and Chandra Theesfeld.\u00a0<\/span><\/p>\n<p><i><span style=\"font-weight: 400\">Photo by<\/span><\/i><\/p>\n<p><i><span style=\"font-weight: 400\">Denise Applewhite, Office of Communications<\/span><\/i><\/p>\n<p><i><span style=\"font-weight: 400\">The paper, \u201c<\/span><\/i><a href=\"https:\/\/www.nature.com\/articles\/s41588-025-02224-z\" target=\"_blank\" rel=\"nofollow noopener\"><i><span style=\"font-weight: 400\">Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs<\/span><\/i><\/a><i><span style=\"font-weight: 400\">,\u201d was published July 9 in Nature Genetics. In addition to Litman, Sauerwald, Foss-Feig, Theesfeld and Troyanskaya, co-authors include LeeAnne Green Snyder of the Simons Foundation, Christopher Y. Park and Yun Hao of the Flatiron Institute, and Ilan Dinstein of Ben Gurion University of the Negev, who contributed to the study during a sabbatical at the Simons Foundation. The research was supported in part by the U.S. National Institutes of Health and the Simons Foundation.<\/span><\/i><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Researchers at Princeton University and the Simons Foundation have identified four clinically and biologically distinct subtypes of autism, marking a transformative step in understanding the condition\u2019s genetic underpinnings and potential for personalized care Analyzing data from over 5,000 children in\u00a0SPARK, an autism cohort study funded by the Simons Foundation, the researchers used a computational model\u2026<\/p>\n","protected":false},"author":2,"featured_media":20141,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_scj_primary_category_id":98,"_scj_featured":false,"_scj_featured_from":"","_scj_featured_until":"","_scj_featured_order":0,"_scj_visibility_class":"current","_scj_layout_family":"standard","_scj_article_style":"","_scj_display_overrides":[],"_scj_intro_image_id":20141,"_scj_intro_alt":"Major autism study uncovers biologically distinct subtypes, paving the way for precision diagnosis and care","_scj_intro_caption":"","_scj_intro_class":"","_scj_intro_float":"","_scj_full_image_id":20141,"_scj_full_alt":"Major autism study uncovers biologically distinct subtypes, paving the way for precision diagnosis and 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