Joshua K Lee1, Derek S Andrews1, Sally Ozonoff1, Marjorie Solomon1, Sally Rogers1, David G Amaral2, Christine Wu Nordahl3. 1. MIND Institute, University of California Davis School of Medicine, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California. 2. MIND Institute, University of California Davis School of Medicine, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California. Electronic address: dgamaral@ucdavis.edu. 3. MIND Institute, University of California Davis School of Medicine, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California. Electronic address: cnordahl@ucdavis.edu.
Abstract
BACKGROUND: Cerebral overgrowth is frequently reported in children but not in adults with autism spectrum disorder (ASD). This suggests that early cerebral overgrowth is followed by normalization of cerebral volumes. However, this notion is predicated on cross-sectional research that is vulnerable to sampling bias. For example, autistic individuals with disproportionate megalencephaly, a subgroup with higher rates of intellectual disability and larger cerebral volumes, may be underrepresented in studies of adolescents and adults. Furthermore, extant studies have cohorts that are predominately male, thus limiting knowledge of cerebral growth in females with ASD. METHODS: Growth of total cerebral volume, gray matter (GM) volume, and white matter volume as well as proportion of GM to total cerebral volume were examined in a longitudinal sample comprising 273 boys (199 with ASD) scanned at up to four time points (mean ages = 38, 50, 64, and 137 months, respectively) and 156 girls (95 with ASD) scanned at up to three time points (mean ages = 39, 53, and 65 months, respectively) using mixed-effects modeling. RESULTS: In boys with ASD, cerebral overgrowth in the ASD with disproportionate megalencephaly subgroup was predominately driven by increases in GM and persisted throughout childhood without evidence of volumetric regression or normalization. In girls with ASD, cerebral volumes were similar to those in typically developing girls, but growth trajectories of GM and white matter were slower throughout early childhood. The proportion of GM to total cerebral volume declined with age at a slower rate in autistic boys and girls relative to typically developing control subjects. CONCLUSIONS: Longitudinal evidence does not support the notion that early brain overgrowth is followed by volumetric regression, at least from early to late childhood.
BACKGROUND: Cerebral overgrowth is frequently reported in children but not in adults with autism spectrum disorder (ASD). This suggests that early cerebral overgrowth is followed by normalization of cerebral volumes. However, this notion is predicated on cross-sectional research that is vulnerable to sampling bias. For example, autistic individuals with disproportionate megalencephaly, a subgroup with higher rates of intellectual disability and larger cerebral volumes, may be underrepresented in studies of adolescents and adults. Furthermore, extant studies have cohorts that are predominately male, thus limiting knowledge of cerebral growth in females with ASD. METHODS: Growth of total cerebral volume, gray matter (GM) volume, and white matter volume as well as proportion of GM to total cerebral volume were examined in a longitudinal sample comprising 273 boys (199 with ASD) scanned at up to four time points (mean ages = 38, 50, 64, and 137 months, respectively) and 156 girls (95 with ASD) scanned at up to three time points (mean ages = 39, 53, and 65 months, respectively) using mixed-effects modeling. RESULTS: In boys with ASD, cerebral overgrowth in the ASD with disproportionate megalencephaly subgroup was predominately driven by increases in GM and persisted throughout childhood without evidence of volumetric regression or normalization. In girls with ASD, cerebral volumes were similar to those in typically developing girls, but growth trajectories of GM and white matter were slower throughout early childhood. The proportion of GM to total cerebral volume declined with age at a slower rate in autistic boys and girls relative to typically developing control subjects. CONCLUSIONS: Longitudinal evidence does not support the notion that early brain overgrowth is followed by volumetric regression, at least from early to late childhood.
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