Unsupervised data-driven stratification of mentalizing heterogeneity in autism

Michael V. Lombardo, Meng-Chuan Lai, Bonnie Auyeung, Rosemary J. Holt, Carrie Allison, Paula Smith, Bhismadev Chakrabarti, Amber N. V. Ruigrok, John Suckling, Edward T. Bullmore, Christine Ecker, Michael Craig, Declan G M Murphy, Francesca Happé, Simon Baron-Cohen

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number35333
JournalScientific Reports
Publication statusPublished - 18 Oct 2016


  • autism
  • clustering
  • precision medicine
  • mentalizing
  • emotion recognition
  • heterogeneity

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