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dc.contributor.authorEcker, Christineen
dc.contributor.authorAndrews, Derek Sen
dc.contributor.authorGudbrandsen, Christina Men
dc.contributor.authorMarquand, Andre Fen
dc.contributor.authorGinestet, Cedric Een
dc.contributor.authorDaly, Eileen Men
dc.contributor.authorMurphy, Clodagh Men
dc.contributor.authorLai, Meng-Chuanen
dc.contributor.authorLombardo, Michael Ven
dc.contributor.authorRuigrok, Amberen
dc.contributor.authorBullmore, Edwarden
dc.contributor.authorSuckling, Johnen
dc.contributor.authorWilliams, Steven CRen
dc.contributor.authorBaron-Cohen, Simonen
dc.contributor.authorCraig, Michael Cen
dc.contributor.authorMurphy, Declan GMen
dc.contributor.authorMedical Research Council Autism Imaging Multicentre Study (MRC AIMS) Consortium,en
dc.date.accessioned2017-08-16T11:48:24Z
dc.date.available2017-08-16T11:48:24Z
dc.date.issued2017-04en
dc.identifier.issn2168-622X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266495
dc.description.abstractImportance: Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive. Objectives: To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD. Design, Setting, and Participants: This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016. Main Outcomes and Measures: Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals. Results: Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P = .72 vs .24, respectively; χ21 = 20.26; P < .001; difference in P values, 0.48; 95% CI, 0.29-0.68). This finding translates to an estimated variability in population prevalence from 0.2% to 1.3%, respectively. Moreover, the patterns of neuroanatomical variability carrying low or high ASD probability were sex specific (eg, in inferior temporal regions, where ASD has different neurobiological underpinnings in male individuals and female individuals). Conclusions and Relevance: These findings highlight the need for considering normative sex-related phenotypic diversity when determining an individual's risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence.
dc.format.mediumPrinten
dc.languageengen
dc.language.isoenen
dc.subjectMedical Research Council Autism Imaging Multicentre Study (MRC AIMS) Consortiumen
dc.subjectCerebral Cortexen
dc.subjectHumansen
dc.subjectImage Interpretation, Computer-Assisteden
dc.subjectMagnetic Resonance Imagingen
dc.subjectImage Enhancementen
dc.subjectMultivariate Analysisen
dc.subjectModels, Statisticalen
dc.subjectRisk Factorsen
dc.subjectCase-Control Studiesen
dc.subjectCross-Sectional Studiesen
dc.subjectSex Characteristicsen
dc.subjectPhenotypeen
dc.subjectReference Valuesen
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectYoung Adulten
dc.subjectWhite Matteren
dc.subjectGray Matteren
dc.subjectAutism Spectrum Disorderen
dc.titleAssociation Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure.en
dc.typeArticle
prism.endingPage338
prism.issueIdentifier4en
prism.publicationDate2017en
prism.publicationNameJAMA psychiatryen
prism.startingPage329
prism.volume74en
dc.identifier.doi10.17863/CAM.12325
dcterms.dateAccepted2016-12-01en
rioxxterms.versionofrecord10.1001/jamapsychiatry.2016.3990en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-04en
dc.contributor.orcidGudbrandsen, Christina M [0000-0002-0464-2065]
dc.contributor.orcidMarquand, Andre F [0000-0001-5903-203X]
dc.contributor.orcidLai, Meng-Chuan [0000-0002-9593-5508]
dc.contributor.orcidRuigrok, Amber [0000-0001-7711-8056]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.contributor.orcidSuckling, John [0000-0002-5098-1527]
dc.contributor.orcidWilliams, Steven CR [0000-0003-4299-1941]
dc.contributor.orcidBaron-Cohen, Simon [0000-0001-9217-2544]
dc.contributor.orcidCraig, Michael C [0000-0002-5311-8673]
dc.identifier.eissn2168-6238
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idAutism Research Trust (unknown)
rioxxterms.freetoread.startdate2018-08-25


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