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      The “Reading the Mind in the Eyes” Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism

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          The “Reading the Mind in the Eyes” test (Eyes test) is an advanced test of theory of mind. Typical sex difference has been reported (i.e., female advantage). Individuals with autism show more difficulty than do typically developing individuals, yet it remains unclear how this is modulated by sex, as females with autism have been under-represented. Here in a large, non-male-biased sample we test for the effects of sex, diagnosis, and their interaction. The Eyes test (revised version) was administered online to 395 adults with autism (178 males, 217 females) and 320 control adults (152 males, 168 females). Two-way ANOVA showed a significant sex-by-diagnosis interaction in total correct score (F(1,711) = 5.090, p = 0.024, η p 2 = 0.007) arising from a significant sex difference between control males and females ( p < 0.001, Cohen’s d = 0.47), and an absence of a sex difference between males and females with autism ( p = 0.907, d = 0.01); significant case-control differences were observed across sexes, with effect sizes of d = 0.35 in males and d = 0.69 in females. Group-difference patterns fit with the extreme-male-brain (EMB) theory predictions. Eyes test-Empathy Quotient and Eyes test-Autism Spectrum Quotient correlations were significant only in females with autism ( r = 0.35, r = -0.32, respectively), but not in the other 3 groups. Support vector machine (SVM) classification based on response pattern across all 36 items classified autism diagnosis with a relatively higher accuracy for females (72.2%) than males (65.8%). Nevertheless, an SVM model trained within one sex generalized equally well when applied to the other sex. Performance on the Eyes test is a sex-independent phenotypic characteristic of adults with autism, reflecting sex-common social difficulties, and provides support for the EMB theory predictions for both males and females. Performance of females with autism differed from same-sex controls more than did that of males with autism. Females with autism also showed stronger coherence between self-reported dispositional traits and Eyes test performance than all other groups.

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          Most cited references 61

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          Sex differences in the brain: implications for explaining autism.

          Empathizing is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior of nonagentive deterministic systems by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males are stronger systemizers. The "extreme male brain" theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy may also be extremes of typical male neuroanatomy.
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            The eye contact effect: mechanisms and development.

            The 'eye contact effect' is the phenomenon that perceived eye contact with another human face modulates certain aspects of the concurrent and/or immediately following cognitive processing. In addition, functional imaging studies in adults have revealed that eye contact can modulate activity in structures in the social brain network, and developmental studies show evidence for preferential orienting towards, and processing of, faces with direct gaze from early in life. We review different theories of the eye contact effect and advance a 'fast-track modulator' model. Specifically, we hypothesize that perceived eye contact is initially detected by a subcortical route, which then modulates the activation of the social brain as it processes the accompanying detailed sensory information.
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              The role of age and verbal ability in the theory of mind task performance of subjects with autism.

               F Happé (1995)
              A number of studies have reported that most children with autism fail theory of mind tasks. It is unclear why certain children with autism pass such tests and what might be different about these subjects. In the present study, the role of age and verbal ability in theory of mind task performance was explored. Data were pooled from 70 autistic, 34 mentally handicapped, and 70 normal young subjects, previously tested for a number of different studies. The analysis suggested that children with autism required far higher verbal mental age to pass false belief tasks than did other subjects. While normally developing children had a 50% probability of passing both tasks at the verbal mental age of 4 years, autistic subjects took more than twice as long to reach this probability of success (at the advanced verbal mental age of 9-2). Possible causal relations between verbal ability and the ability to represent mental states are discussed.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                27 August 2015
                : 10
                : 8
                [1 ]Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
                [2 ]CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom
                [3 ]Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom
                [4 ]Department of Psychology and Center of Applied Neuroscience, University of Cyprus, Nicosia, Cyprus
                [5 ]Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Canada
                [6 ]Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
                University of Tokyo, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SB-C DCB RJH CA BA M-CL. Performed the experiments: SB-C DCB RJH CA BA MVL PS M-CL. Analyzed the data: DCB CA MVL PS M-CL. Contributed reagents/materials/analysis tools: SB-C CA BA MVL PS M-CL. Wrote the paper: SB-C DCB RJH CA BA MVL PS M-CL.


                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                Page count
                Figures: 1, Tables: 1, Pages: 17
                The study was funded by grants from the UK Medical Research Council (G0600977,, the Wellcome Trust (091774/Z/10/Z,, and the Autism Research Trust ( to SB-C. The research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care - East of England (CLAHRC-EoE). M-CL was supported by the William Binks Autism Neuroscience Fellowship during the period of this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Custom metadata
                Volunteers in the Cambridge Autism Research Database (CARD) did not consent for their data to be deposited in an Open Access archive. However, the CARD Management Committee considers requests by researchers for specific parts of the database (in anonymized form) to test specific hypotheses (please contact: info@ ). For access to data used in this paper specifically, please contact Dr. Meng-Chuan Lai ( mcl45@ ).



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