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      Brain and behavior development in autism from birth through infancy Translated title: Desarrollo conductual y cerebral en el autism entre el nacimiento y la infancia Translated title: Developpement du cerveau et du comportement dans l'autisme de la naissance à la petite enfance

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          Abstract

          Autism spectrum disorder (ASD) is a heterogeneous condition that affects 1 in 68 children. Diagnosis is based on the presence of characteristic behavioral impairments that emerge in the second year of life and thus is not typically made until 3 to 4 years of age. Recent studies of early brain and behavior development have provided important new insights into the nature of this condition. Autism-specific brain imaging features have been identified as early as 6 months of age, and age-specific brain and behavior changes have been demonstrated across the first 2 years of life, highlighting the developmental nature of ASD. New findings demonstrate that early brain imaging in the first year of life holds great promise for presymptomatic prediction of ASD. There is a general understanding in medicine that earlier treatment has better outcomes than later treatment, and in autism, there is an emerging consensus that earlier intervention results in more successful outcomes for the child. Examining early brain and behavior trajectories also has the potential to parse the etiologic heterogeneity in ASD, a well-recognized impediment to developing targeted, mechanistic treatments. This review highlights the current state of the science in the pursuit of early brain and behavioral markers of autism during infancy and examines the potential implications of these findings for treatment of this condition.

          Translated abstract

          El trastorno del espectro autista (TEA) es una condición heterogénea que afecta a uno entre 68 niños. El diagnóstico está basado en la presencia de alteraciones conductuales características que aparecen durante el segundo año de vida y que no son totalmente típicas hasta los tres o cuatro años. Estudios recientes sobre el desarrollo precoz, tanto cerebral como conductual, han aportado novedosos conocimientos respecto a la naturaleza de este cuadro. En los estudios de imágenes, ya a los seis meses de edad se han identificado características que son específicas para el autismo; también se han observado cambios conductuales y cerebrales específicos para la edad durante los dos primeros años de vida, lo que resalta la naturaleza evolutiva del TEA. Hay nuevos hallazgos que demuestran que imágenes cerebrales precoces durante el primer año de vida constituyen una gran promesa para la predicción del TEA previo a la aparición de los síntomas. En medicina existe el concepto que un tratamiento más precoz tiene mejor resultado que uno más tardío, y en el autismo ha surgido el consenso que una intervención más precoz obtiene resultados más exitosos para el niño. La evaluación de las manifestaciones conductuales y cerebrales precoces también tiene el potencial de analizar la heterogeneidad etiológica del TEA, la cual constituye un impedimento bien reconocido para el desarrollo de tratamientos específicos. Esta revisión destaca el estado actual de la ciencia en cuanto a la búsqueda de marcadores conductuales y cerebrales precoces de autismo durante la infancia y analiza las potenciales implicancias de estos hallazgos en el tratamiento de esta patología.

          Translated abstract

          Le trouble du spectre de l'autisme (TSA) est une maladie hétérogène qui touche 1 enfant sur 68. Le diagnostic, rarement posé avant 3 ou 4 ans, est basé sur la présence de déficits comportementaux caractéristiques, apparaissant lors de la deuxième année de vie. De récentes études sur le développement précoce du cerveau et du comportement ont éclairé différemment la nature de cette maladie. Une imagerie cérébrale spécifique de l'autisme est identifiée dès l'âge de 6 mois et les modifications du cerveau et du comportement liées à l'âge mises en évidence lors des 2 premières années de vie, soulignent la nature développementale du TSA. D'après des données récentes, l'imagerie cérébrale précoce dans la 1 re année de vie est très prometteuse en termes de prédiction présymptomatique du TSA. En médecine, il est généralement admis qu'un traitement précoce donne de meilleurs résultats qu'un traitement tardif et dans l'autisme, le consensus actuel est qu'il est bénéfique pour l'enfant d'intervenir tôt. L'examen des trajectoires précoces du cerveau et du comportement permet d'analyser l'hétérogénéité étiologique du TSA, frein bien connu au développement de traitements mécanistiques ciblés. Cet article met en lumière l'état actuel de la science dans la recherche de marqueurs précoces cérébraux et comportementaux de l'autisme pendant l'enfance et il analyse les implications potentielles de ces résultats pour le traitement de cette maladie.

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          Distinct genetic influences on cortical surface area and cortical thickness.

          Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
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            Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study.

            To quantify developmental abnormalities in cerebral and cerebellar volume in autism. The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable. Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI-VII than normal controls. Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.
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              A structural MRI study of human brain development from birth to 2 years.

              Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.
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                Author and article information

                Contributors
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                December 2017
                December 2017
                : 19
                : 4
                : 325-333
                Affiliations
                Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
                Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
                Author notes
                Article
                10.31887/DCNS.2017.19.4/mshen
                5789210
                29398928
                08bd210b-b08a-4d01-aad5-5e2006eba09d
                Copyright: © 2017 AICH - Servier Research Group. All rights reserved

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                State of the Art

                Neurosciences
                autism,autism spectrum disorder,cortical surface area,biomarker,brain development,diffusion tensor imaging,early detection,early prediction,early risk sign,extra-axial cerebrospinal fluid,functional connectivity,infancy

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