title: Unsupervised data-driven stratification of mentalizing heterogeneity in autism.
abstract: 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 effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.
authors.affiliation: Center for Applied Neuroscience, Department of Psychology, University of Cyprus, Nicosia, Cyprus.|Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Lombardo
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Department of Psychiatry, University of Toronto, Toronto, Canada.|Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|School of Philosophy, Psychology and Language Sciences, Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Auyeung
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Holt
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Carrie
authors.initials: C
authors.lastname: Allison
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Smith
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
authors.forename: Bhismadev
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Amber N V
authors.initials: AN
authors.lastname: Ruigrok
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Child &Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ecker
authors.affiliation: Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|National Autism Unit, Bethlem Royal Hospital, SLAM NHS Foundation Trust, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Craig
authors.affiliation: Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy
authors.affiliation: MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Happé
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D004644:Emotions / Q000502:physiology; D005260:Female; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011932:Reading; D049490:Systems Biology / Q000379:methods; D055815:Young Adult