{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T20:01:31Z","timestamp":1776542491864,"version":"3.51.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>Germline heterozygous <jats:italic>PTEN<\/jats:italic> mutations have been associated with high prevalence of autism spectrum disorder (ASD) and elevated rates and severity of broadly defined behavioral problems. However, limited progress has been made toward understanding whether <jats:italic>PTEN<\/jats:italic> mutation is associated with specific psychiatric co-morbidity profiles when compared to idiopathic ASD. The current study aimed to utilize a cross-measure approach to compare concurrent psychiatric characteristics across children and adolescents with <jats:italic>PTEN<\/jats:italic> mutation with (<jats:italic>PTEN<\/jats:italic>-ASD; <jats:italic>n<\/jats:italic> = 38) and without ASD (<jats:italic>PTEN<\/jats:italic>-No ASD; <jats:italic>n<\/jats:italic> = 23), and ASD with macrocephaly but no <jats:italic>PTEN<\/jats:italic> mutation (macro-ASD; <jats:italic>n<\/jats:italic> = 25) using the Child Behavior Checklist (CBCL) and the Aberrant Behavior Checklist (ABC). There were significant group effects for the CBCL Internalizing and Externalizing broad symptom score, the majority of specific CBCL syndrome scores, and all ABC subscale scores. <jats:italic>Post-hoc<\/jats:italic> comparisons revealed greater behavioral symptoms in the ASD groups (<jats:italic>PTEN<\/jats:italic>-ASD and macro-ASD) compared to the <jats:italic>PTEN<\/jats:italic>-no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the <jats:italic>PTEN<\/jats:italic>-ASD and macro-ASD groups; however, there was a trend for the macro-ASD group showing higher levels of aggressive behaviors. Our findings provide evidence of specific behavior profiles across <jats:italic>PTEN<\/jats:italic>-No ASD, <jats:italic>PTEN<\/jats:italic>-ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with <jats:italic>PTEN<\/jats:italic> mutations in order to provide access to appropriate evidence-based interventions.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.672070","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T11:44:32Z","timestamp":1629200672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Psychiatric Characteristics Across Individuals With PTEN Mutations"],"prefix":"10.3389","volume":"12","author":[{"given":"Morgan","family":"Steele","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirko","family":"Uljarevi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga\u00eblle","family":"Rached","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Frazier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin A.","family":"Libove","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn M.","family":"Busch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Klaas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian A.","family":"Martinez-Agosto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Y.","family":"Hardan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/gim.2013.1","article-title":"Cognitive characteristics of PTEN hamartoma tumor syndromes","volume":"15","author":"Busch","year":"2013","journal-title":"Genet Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-019-0588-1","article-title":"Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN","volume":"9","author":"Busch","year":"2019","journal-title":"Transl Psychiatry."},{"key":"B3","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1136\/jmedgenet-2016-104484","article-title":"A retrospective chart review of the features of PTEN hamartoma tumour syndrome in children","volume":"54","author":"Hansen-Kiss","year":"2017","journal-title":"J Med Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1158\/1078-0432.CCR-11-2283","article-title":"Lifetime cancer risks in individuals with germline PTEN mutations","volume":"18","author":"Tan","year":"2012","journal-title":"Clin Cancer Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1136\/jmg.2004.024646","article-title":"Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations","volume":"42","author":"Butler","year":"2005","journal-title":"J Med Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1002\/ajmg.b.30493","article-title":"Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly","volume":"144","author":"Buxbaum","year":"2007","journal-title":"Am J Med Genet B: Neuropsychiatr Genet."},{"key":"B7","first-page":"187","article-title":"Macrocephaly and megalencephaly in autism spectrum disorder","volume-title":"Autism Imaging and Devices","author":"Libero","year":"2017"},{"key":"B8","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1007\/s13311-015-0356-8","article-title":"Balancing proliferation and connectivity in PTEN-associated autism spectrum disorder","volume":"12","author":"Tilot","year":"2015","journal-title":"Neurotherapeutics."},{"key":"B9","doi-asserted-by":"publisher","first-page":"103596","DOI":"10.1016\/j.ejmg.2018.12.001","article-title":"Clinical spectrum of PTEN mutation in pediatric patients. 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