biostudies-literatureLombardo MVMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust35333https://www.ebi.ac.uk/biostudies/studies/S-EPMC5067562biostudies-literatureUnknown6Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n = 694; n = 249), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 45-62% of ASC adults show evidence for large impairments (Cohen's d = -1.03 to -11.21), while other subgroups are effectivScientific reportsUnsupervised data-driven stratification of mentalizing heterogeneity in autism.PMC5067562091774/Z/10/ZG0600977RP-PG-0606-1045NF-SI-0515-10097MR/N026063/1NF-SI-0513-10051G9817803BG9817803G1000183G1000183B093875MRC AIMS ConsortiumSpain DMurphy CMEllie Wilson CDaly EMChakrabarti BBullmore ETJones DKCraig MCCarrington SHolt RJAllison CLombardo MVJezzard PWilliams SCRuigrok ANBailey AJBaron-Cohen SSuckling JStewart RAuyeung BBolton PFDeoni SCWheelwright SJEcker CMullins DPasco GSmith PSadek SAMadden ACatani MLai MCHappe FMurphy DGJohnston PHenty JfalseUnsupervised data-driven stratification of mentalizing heterogeneity in autism.Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n = 694; n = 249), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 45-62% of ASC adults show evidence for large impairments (Cohen's d = -1.03 to -11.21), while other subgroups are effectiv2016-01-01T00:00:00Z2016 Oct2025-04-27T01:56:19.106Z2019-03-27T02:26:54ZS-EPMC50675622775205410.1038/srep35333