Assessment of Neuroanatomical Endophenotypes of Autism Spectrum Disorder and Association With Characteristics of Individuals With Schizophrenia and the General Population

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorHWANG, Gyujoon
dc.contributor.authorWEN, Junhao
dc.contributor.authorSOTARDI, Susan
dc.contributor.authorBRODKIN, Edward S.
dc.contributor.authorCHAND, Ganesh B.
dc.contributor.authorDWYER, Dominic B.
dc.contributor.authorERUS, Guray
dc.contributor.authorDOSHI, Jimit
dc.contributor.authorSINGHAL, Pankhuri
dc.contributor.authorSRINIVASAN, Dhivya
dc.contributor.authorVAROL, Erdem
dc.contributor.authorSOTIRAS, Aristeidis
dc.contributor.authorDAZZAN, Paola
dc.contributor.authorKAHN, Rene S. S.
dc.contributor.authorSCHNACK, Hugo G. G.
dc.contributor.authorZANETTI, Marcus V. V.
dc.contributor.authorMEISENZAHL, Eva
dc.contributor.authorBUSATTO, Geraldo F. F.
dc.contributor.authorCRESPO-FACORRO, Benedicto
dc.contributor.authorPANTELIS, Christos
dc.contributor.authorWOOD, Stephen J. J.
dc.contributor.authorZHUO, Chuanjun
dc.contributor.authorSHINOHARA, Russell T. T.
dc.contributor.authorSHOU, Haochang
dc.contributor.authorFAN, Yong
dc.contributor.authorMARTINO, Adriana Di
dc.contributor.authorKOUTSOULERIS, Nikolaos
dc.contributor.authorGUR, Raquel E. E.
dc.contributor.authorGUR, Ruben C. C.
dc.contributor.authorSATTERTHWAITE, Theodore D. D.
dc.contributor.authorWOLF, Daniel H. H.
dc.contributor.authorDAVATZIKOS, Christos
dc.date.accessioned2023-06-21T14:15:13Z
dc.date.available2023-06-21T14:15:13Z
dc.date.issued2023
dc.description.abstractIMPORTANCE Autism spectrum disorder (ASD) is associated with significant clinical, neuroanatomical, and genetic heterogeneity that limits precision diagnostics and treatment. OBJECTIVE To assess distinct neuroanatomical dimensions of ASD using novel semisupervised machine learningmethods and to test whether the dimensions can serve as endophenotypes also in non-ASD populations. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used imaging data from the publicly available Autism Brain Imaging Data Exchange (ABIDE) repositories as the discovery cohort. The ABIDE sample included individuals diagnosed with ASD aged between 16 and 64 years and age- and sex-match typically developing individuals. Validation cohorts included individuals with schizophrenia from the Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging (PHENOM) consortium and individuals from the UK Biobank to represent the general population. The multisite discovery cohort included 16 internationally distributed imaging sites. Analyses were performed between March 2021 and March 2022. MAIN OUTCOMES AND MEASURES The trained semisupervised heterogeneity through discriminative analysis models were tested for reproducibility using extensive cross-validations. It was then applied to individuals from the PHENOM and the UK Biobank. It was hypothesized that neuroanatomical dimensions of ASD would display distinct clinical and genetic profiles and would be prominent also in non-ASD populations. RESULTS Heterogeneity through discriminative analysis models trained on T1-weighted brain magnetic resonance images of 307 individuals with ASD (mean [SD] age, 25.4 [9.8] years; 273 [88.9%] male) and 362 typically developing control individuals (mean [SD] age, 25.8 [8.9] years; 309 [85.4%] male) revealed that a 3-dimensional scheme was optimal to capture the ASD neuroanatomy. The first dimension (A1: aginglike) was associated with smaller brain volume, lower cognitive function, and aging-related genetic variants (FOXO3; Z = 4.65; P = 1.62 x 10(-6)). The second dimension (A2: schizophrenialike) was characterized by enlarged subcortical volumes, antipsychotic medication use (Cohen d = 0.65; false discovery rate-adjusted P =.048), partially overlapping genetic, neuroanatomical characteristics to schizophrenia (n = 307), and significant genetic heritability estimates in the general population (n = 14 786; mean [SD] h2, 0.71 [0.04]; P < 1 x 10(-4)). The third dimension (A3: typical ASD) was distinguished by enlarged cortical volumes, high nonverbal cognitive performance, and biological pathways implicating brain development and abnormal apoptosis (mean [SD] beta, 0.83 [0.02]; P = 4.22 x 10(-6)). CONCLUSIONS AND RELEVANCE This cross-sectional study discovered 3-dimensional endophenotypic representation that may elucidate the heterogeneous neurobiological underpinnings of ASD to support precision diagnostics. The significant correspondence between A2 and schizophrenia indicates a possibility of identifying common biological mechanisms across the 2 mental health diagnoses.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.identifier.citationJAMA PSYCHIATRY, v.80, n.5, p.498-507, 2023
dc.identifier.doi10.1001/jamapsychiatry.2023.0409
dc.identifier.eissn2168-6238
dc.identifier.issn2168-622X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/54026
dc.language.isoeng
dc.publisherAMER MEDICAL ASSOCeng
dc.relation.ispartofJama Psychiatry
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright AMER MEDICAL ASSOCeng
dc.subject.otherheterogeneityeng
dc.subject.otherasdeng
dc.subject.wosPsychiatryeng
dc.titleAssessment of Neuroanatomical Endophenotypes of Autism Spectrum Disorder and Association With Characteristics of Individuals With Schizophrenia and the General Populationeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryEspanha
hcfmusp.affiliation.countryAustrália
hcfmusp.affiliation.countryChina
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countryAlemanha
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisode
hcfmusp.affiliation.countryisogb
hcfmusp.affiliation.countryisonl
hcfmusp.affiliation.countryisoes
hcfmusp.affiliation.countryisoau
hcfmusp.affiliation.countryisocn
hcfmusp.author.externalHWANG, Gyujoon:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, 3700 Hamilton Walk,CBICA,Richards Bldg,7th Floor, Philadelphia, PA 19104 USA
hcfmusp.author.externalWEN, Junhao:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Southern Calif, Stevens Neuroimaging & Informat Inst, Keck Sch Med USC, Lab & Biomed Sci, Marina Del Rey, CA USA
hcfmusp.author.externalSOTARDI, Susan:Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA USA
hcfmusp.author.externalBRODKIN, Edward S.:Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA
hcfmusp.author.externalCHAND, Ganesh B.:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Washington Univ, Sch Med, Dept Radiol, St Louis, MO USA
hcfmusp.author.externalDWYER, Dominic B.:Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Munich, Germany
hcfmusp.author.externalERUS, Guray:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA
hcfmusp.author.externalDOSHI, Jimit:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA
hcfmusp.author.externalSINGHAL, Pankhuri:Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA USA
hcfmusp.author.externalSRINIVASAN, Dhivya:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA
hcfmusp.author.externalVAROL, Erdem:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Columbia Univ, Zuckerman Inst, Dept Stat, New York, NY USA
hcfmusp.author.externalSOTIRAS, Aristeidis:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Washington Univ, Sch Med, Dept Radiol, St Louis, MO USA
hcfmusp.author.externalDAZZAN, Paola:Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London, England
hcfmusp.author.externalKAHN, Rene S. S.:Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA
hcfmusp.author.externalSCHNACK, Hugo G. G.:Univ Med Ctr Utrecht, Dept Psychiat, Utrecht, Netherlands
hcfmusp.author.externalZANETTI, Marcus V. V.:Univ Sao Paulo, Inst Psychiat, Fac Med, Sao Paulo, Brazil; Hosp Sirio Libanes, Sao Paulo, Brazil
hcfmusp.author.externalMEISENZAHL, Eva:Kliniken Heinrich Heine Univ, LVR Klinikum Dusseldorf, Dusseldorf, Germany
hcfmusp.author.externalCRESPO-FACORRO, Benedicto:Univ Seville, Univ Hosp Virgen Rocio, Sch Med, Dept Psychiat,IBiS,CIBERSAM, Seville, Spain
hcfmusp.author.externalPANTELIS, Christos:Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Carlton, Vic, Australia; Melbourne Hlth, Carlton, Vic, Australia
hcfmusp.author.externalWOOD, Stephen J. J.:Orygen, Melbourne, Vic, Australia; Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia; Univ Birmingham, Sch Psychol, Edgbaston, England
hcfmusp.author.externalZHUO, Chuanjun:Tianjin Anding Hosp, Dept Psychiat Neuroimaging Genet & Comorbid Lab, Tianjin, Peoples R China; Tianjin Med Univ, Dept Psychiat, Tianjin, Peoples R China
hcfmusp.author.externalSHINOHARA, Russell T. T.:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, Penn Stat Imaging & Visualizat Ctr, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA USA
hcfmusp.author.externalSHOU, Haochang:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, Penn Stat Imaging & Visualizat Ctr, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA USA
hcfmusp.author.externalFAN, Yong:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA
hcfmusp.author.externalMARTINO, Adriana Di:NYU, Phyllis Green & Randolph Cowen Inst Pediat Neurosc, Child Study Ctr, New York, NY USA
hcfmusp.author.externalKOUTSOULERIS, Nikolaos:Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Munich, Germany
hcfmusp.author.externalGUR, Raquel E. E.:Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA
hcfmusp.author.externalGUR, Ruben C. C.:Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA
hcfmusp.author.externalSATTERTHWAITE, Theodore D. D.:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA
hcfmusp.author.externalWOLF, Daniel H. H.:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA
hcfmusp.author.externalDAVATZIKOS, Christos:Univ Penn, Perelman Sch Med, Ctr Data Sci Integrated Diagnost AI2D, Philadelphia, PA 19104 USA; Univ Penn, Perelman Sch Med, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA; Univ Penn, 3700 Hamilton Walk,CBICA,Richards Bldg,7th Floor, Philadelphia, PA 19104 USA
hcfmusp.citation.scopus3
hcfmusp.contributor.author-fmusphcGERALDO BUSATTO FILHO
hcfmusp.description.beginpage498
hcfmusp.description.endpage507
hcfmusp.description.issue5
hcfmusp.description.volume80
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hcfmusp.origem.pubmed37017948
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