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Psychiatric Characteristics Across Individuals With PTEN Mutations

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journal contribution
posted on 06.10.2021, 06:55 by M Steele, Mirko UljarevicMirko Uljarevic, G Rached, TW Frazier, JM Phillips, RA Libove, RM Busch, P Klaas, JA Martinez-Agosto, S Srivastava, C Eng, M Sahin, AY Hardan
Germline heterozygous PTEN 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 PTEN 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 PTEN mutation with (PTEN-ASD; n = 38) and without ASD (PTEN-No ASD; n = 23), and ASD with macrocephaly but no PTEN mutation (macro-ASD; n = 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. Post-hoc comparisons revealed greater behavioral symptoms in the ASD groups (PTEN-ASD and macro-ASD) compared to the PTEN-no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the PTEN-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 PTEN-No ASD, PTEN-ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with PTEN mutations in order to provide access to appropriate evidence-based interventions.


This study was funded, in part, by the National Institute of Health Developmental Synaptopathies Consortium (U54NS092090; PI/Network Director: Sahin; Project 2 Leaders/PIs: Eng & Busch) and the Ambrose Monell Foundation (to CE). The Developmental Synaptopathies Consortium (U54NS092090) was part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS). The content was solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). CE was the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic and an ACS Clinical Research Professor. MSa was the Rosamund Stone Zander Chair at Boston Children's Hospital. MU was currently supported by the Australian Research Council Discovery Early Career Researcher Award (DE180100632).


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Frontiers in Psychiatry



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