{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T02:50:41Z","timestamp":1777431041043,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15095.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000}}],"reference-count":55,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["082498"],"award-info":[{"award-number":["082498"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p><ns4:bold>Background<\/ns4:bold>: Recent studies suggest that an extra sex chromosome increases the risk of both autism and social anxiety, but it unclear whether these risks are specific to particular karyotypes.<\/ns4:p><ns4:p> <ns4:bold>Methods<\/ns4:bold>: We considered diagnostic data from an online psychiatric assessment (DAWBA \u2013 The Development and Well-Being Assessment) and questionnaire responses completed by parents of children with 47,XXX (N = 29), 47,XXY (N = 28) and 47,XYY (N = 32) karyotypes. Analysis focused mainly on 54 children who were diagnosed prenatally or on the basis of other medical concerns in childhood (Low Bias subgroup), to minimise ascertainment bias.<\/ns4:p><ns4:p> <ns4:bold>Results<\/ns4:bold>: Children with symptoms of autism who fell short of meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria were coded as cases of Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS). The odds ratio of autism or\u00a0PDDNOS in the Low Bias group was computed relative to gender-specific population norms. This gave log odds ratio (95% confidence interval) of 5.56 (4.25 - 6.88) for XXX girls; 4.00 (2.66 - 5.33) for XXY boys; and 4.60 (3.46 - 5.74) for XYY boys. Despite this elevated risk, most children had no autistic features. A diagnosis of DSM-IV Social Phobia was rare, though, in line with prediction, all three Low Bias cases with this diagnosis had 47,XXY karyotype. All three trisomy groups showed increased risk of milder symptoms of social anxiety.<\/ns4:p><ns4:p> <ns4:bold>Conclusions<\/ns4:bold>: An increased risk of autism was found in girls with 47,XXX karyotype, as well as in boys with 47,XXY or 47,XYY. Symptoms of social anxiety were increased in all three karyotypes. There was wide variation in psychiatric status of children with the same karyotype, suggesting that an extra sex chromosome affects developmental stability in a non-specific way, with a diverse range of possible phenotypes.<\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15095.2","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T07:05:08Z","timestamp":1567407908000},"page":"32","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Autism and social anxiety in children with sex chromosome trisomies: an observational study"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7077-1618","authenticated-orcid":false,"given":"Alexander C.","family":"Wilson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-4033","authenticated-orcid":false,"given":"Dorothy V.M.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"210-5","DOI":"10.1016\/S0140-6736(06)69041-7","article-title":"Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP).","volume":"368","author":"G Baird","year":"2006","journal-title":"Lancet."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"229-242.e21","DOI":"10.1016\/j.cell.2017.03.021","article-title":"Aneuploidy causes non-genetic individuality.","volume":"169","author":"R Beach","year":"2017","journal-title":"Cell."},{"key":"ref-3","article-title":"Language and behavioural phenotypes in children with sex chromosome trisomies","author":"D Bishop","year":"2019"},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.12688\/wellcomeopenres.14904.1","article-title":"Language phenotypes in children with sex chromosome trisomies [version 1; referees: 1 approved].","volume":"3","author":"D Bishop","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"954-959","DOI":"10.1136\/adc.2009.179747","article-title":"Autism, language and communication in children with sex chromosome trisomies.","volume":"96","author":"D Bishop","year":"2011","journal-title":"Arch Dis Child."},{"key":"ref-80","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1136\/bmj.320.7247.1468","article-title":"Statistics notes. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16469.r35140, Armin Raznahan, Developmental Neurogenomics Unit\u00a0(DNU), National Institute of Mental Health\u00a0(NIMH)\u00a0, Bethesda, MD, USA, 08 Apr 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-32\/v1#referee-response-35140","order":0,"name":"referee-response-35140","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Dorothy Bishop<\/b>; \n<i>Posted: 24 Aug 2019<\/i>; Many thanks for the comments on this paper.The point about diagnostic difficulty is very pertinent, and a paragraph has been added to the latest version of the paper, giving a couple of illustrative vignettes.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-32\/v2#referee-comment-3933","order":1,"name":"referee-comment-3933","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16469.r35468, Jobst Meyer, Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany, 03 Jun 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-32\/v1#referee-response-35468","order":2,"name":"referee-response-35468","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Dorothy Bishop<\/b>; \n<i>Posted: 24 Aug 2019<\/i>; Many thanks for your careful reading of this paper. We have made clarifications and corrections as you suggested, plus a further comment on the rates of impairment in females with trisomy X in the latest version of the paper.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-32\/v2#referee-comment-3934","order":3,"name":"referee-comment-3934","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by the Wellcome Trust through a Programme Grant to DB [082498]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}