Charlotte M Pretzsch,Martina Arenella,Jason P Lerch,Michael V Lombardo,Christian Beckmann,Tim Schaefer,Johanna Leyhausen,Caroline Gurr,Anke Bletsch,Lisa M Berg,Hanna Seelemeyer,Dorothea L Floris,Bethany Oakley,Eva Loth,Thomas Bourgeron,Tony Charman,Jan Buitelaar,Grainne McAlonan,Declan Murphy,Christine Ecker,
{"title":"自闭症患者的大脑成熟模式及其分子关联。","authors":"Charlotte M Pretzsch,Martina Arenella,Jason P Lerch,Michael V Lombardo,Christian Beckmann,Tim Schaefer,Johanna Leyhausen,Caroline Gurr,Anke Bletsch,Lisa M Berg,Hanna Seelemeyer,Dorothea L Floris,Bethany Oakley,Eva Loth,Thomas Bourgeron,Tony Charman,Jan Buitelaar,Grainne McAlonan,Declan Murphy,Christine Ecker,","doi":"10.1001/jamapsychiatry.2024.3194","DOIUrl":null,"url":null,"abstract":"Importance\r\nIn the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.\r\n\r\nObjectives\r\nTo examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.\r\n\r\nDesign, Setting, and Participants\r\nThis study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.\r\n\r\nExposures\r\nNeuroanatomy of neurotypical and autistic participants.\r\n\r\nMain Outcomes and Measures\r\nIntraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.\r\n\r\nResults\r\nA total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.\r\n\r\nConclusions and Relevance\r\nResults of this case-control study suggest that the coordinated development of brain regions was altered in autism, involved a complex interplay of temporally sensitive molecular mechanisms, and may be associated with both lower-order (eg, sensory) and higher-order (eg, social) clinical features of autism. Thus, examining maturational patterns may provide an analytic framework to study the neurobiological origins of clinical profiles in neurodevelopmental/mental health conditions.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"68 1","pages":""},"PeriodicalIF":22.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Patterns of Brain Maturation in Autism and Their Molecular Associations.\",\"authors\":\"Charlotte M Pretzsch,Martina Arenella,Jason P Lerch,Michael V Lombardo,Christian Beckmann,Tim Schaefer,Johanna Leyhausen,Caroline Gurr,Anke Bletsch,Lisa M Berg,Hanna Seelemeyer,Dorothea L Floris,Bethany Oakley,Eva Loth,Thomas Bourgeron,Tony Charman,Jan Buitelaar,Grainne McAlonan,Declan Murphy,Christine Ecker,\",\"doi\":\"10.1001/jamapsychiatry.2024.3194\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Importance\\r\\nIn the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.\\r\\n\\r\\nObjectives\\r\\nTo examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.\\r\\n\\r\\nDesign, Setting, and Participants\\r\\nThis study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.\\r\\n\\r\\nExposures\\r\\nNeuroanatomy of neurotypical and autistic participants.\\r\\n\\r\\nMain Outcomes and Measures\\r\\nIntraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.\\r\\n\\r\\nResults\\r\\nA total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.\\r\\n\\r\\nConclusions and Relevance\\r\\nResults of this case-control study suggest that the coordinated development of brain regions was altered in autism, involved a complex interplay of temporally sensitive molecular mechanisms, and may be associated with both lower-order (eg, sensory) and higher-order (eg, social) clinical features of autism. Thus, examining maturational patterns may provide an analytic framework to study the neurobiological origins of clinical profiles in neurodevelopmental/mental health conditions.\",\"PeriodicalId\":14800,\"journal\":{\"name\":\"JAMA Psychiatry\",\"volume\":\"68 1\",\"pages\":\"\"},\"PeriodicalIF\":22.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAMA Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamapsychiatry.2024.3194\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamapsychiatry.2024.3194","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Patterns of Brain Maturation in Autism and Their Molecular Associations.
Importance
In the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.
Objectives
To examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.
Design, Setting, and Participants
This study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.
Exposures
Neuroanatomy of neurotypical and autistic participants.
Main Outcomes and Measures
Intraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.
Results
A total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.
Conclusions and Relevance
Results of this case-control study suggest that the coordinated development of brain regions was altered in autism, involved a complex interplay of temporally sensitive molecular mechanisms, and may be associated with both lower-order (eg, sensory) and higher-order (eg, social) clinical features of autism. Thus, examining maturational patterns may provide an analytic framework to study the neurobiological origins of clinical profiles in neurodevelopmental/mental health conditions.
期刊介绍:
JAMA Psychiatry is a global, peer-reviewed journal catering to clinicians, scholars, and research scientists in psychiatry, mental health, behavioral science, and related fields. The Archives of Neurology & Psychiatry originated in 1919, splitting into two journals in 1959: Archives of Neurology and Archives of General Psychiatry. In 2013, these evolved into JAMA Neurology and JAMA Psychiatry, respectively. JAMA Psychiatry is affiliated with the JAMA Network, a group of peer-reviewed medical and specialty publications.