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Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Introdução: Estudos prévios de neuroimagem não investigaram de forma abrangente a superfície cortical em indivíduos com esquizofrenia avaliando espessura, área e girificação separadamente entre sujeitos com Primeiro Episódio de Psicose (PEP) e com Esquizofrenia Crônica (EC). Métodos: Investigamos anormalidades da superfície cortical em 137 pacientes com PEP e 240 indivíduos com EC em comparação com 297 Controles Saudáveis (CS), obtidos de seis coortes. Mapas de espessura cortical, área e girificação foram gerados pelo processamento de imagens de ressonância magnética ponderada em T1 utilizando o programa FreeSurfer 5.3, e submetidos a um protocolo de controle de qualidade previamente validado. Além disso, exploramos a contribuição relativa das características sociodemográficas e clínicas para as variações nos índices de superfície cortical em indivíduos com PEP e EC. Resultados: Os sujeitos PEP apresentaram grandes clusters bilaterais de área e de girificação aumentadas em relação aos CS nos córtices pré-frontal e insular (d de Cohen: 0,049 a 0,28). Estas anormalidades se associaram significativamente ao início precoce de doença e ao sexo masculino. Por outro lado, os indivíduos com EC apresentaram espessura cortical reduzida em relação a sujeitos CS em pequenos focos frontotemporais bilateralmente (d: -0,73 a -0,35). Ao menos parcialmente, estas anormalidades se associaram à resistência ao tratamento e ao uso de antipsicóticos de primeira geração (APG). Conclusão: Avaliações separadas de PEP e EC revelaram anormalidades que diferem quanto a distribuição cerebral regional, fenótipos corticais afetados e tamanho do efeito, o que demonstra a necessidade de se decompor a superfície cortical em seus diferentes fenótipos em estudos avaliando estágios distintos da esquizofrenia. Entre sujeitos com PEP, associações de maior área cortical e girificação com idade precoce de início de doença sugerem uma origem em anormalidades do neurodesenvolvimento, enquanto as reduções de espessura entre sujeitos com EC são, ao menos parcialmente, explicadas pela refratariedade ao tratamento e ingestão de APG. Background: Neuroimaging studies so far have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area, and gyrification separately at the first-episode of psychosis (FEP) and during chronic schizophrenia (ChSch). Methods: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by six cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced based on T1-weighted magnetic resonance images using FreeSurfer 5.3, followed by validated quality control protocols. We also explored the relative contribution of sociodemographic and clinical characteristics to variations in cortical surface indices in FEP and ChSch subjects. Results: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohens d: 0.049 to 0.28), with such abnormalities being significantly associated with earlier illness onset and male gender. Conversely, ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d: -0.73 to - 0.35), significantly associated with treatment-resistance and first-generation antipsychotic (FGA) intake. Conclusion: Separate assessments of FEP and ChSch revealed abnormalities that differ by regional brain distribution, cortical phenotypes affected and effect size, highlighting the need to decompose the cortical surface into its different phenotypes in studies evaluating distinct stages of schizophrenia. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake.