When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports

Redcay, Elizabeth; Courchesne, Eric

doi:10.1016/j.biopsych.2005.03.026

Cited by 546 publications

(422 citation statements)

References 58 publications

Supporting

Mentioning

371

Contrasting

Unclassified

Order By: Relevance

“…The importance of the overexpression of a small set of genes including DYRK1A (13 genes) has been recently demonstrated by the observation of a family with 3 cases of partial trisomy 21 (Ronan et al, 2007): the patients present characteristic features of Down syndrome including upslanting palpebral fissures, brachycephaly, and a normal head circumference. Developmental alterations have also been reported in other brain-related diseases: in autism, a 5% increase in total brain weight or total brain volume has been reported, and it has been suggested that these developmental alterations occur in the first few years of life (Redcay and Courchesne, 2005). Based on both these results and our own findings, this approach should be used to investigate other mice models of partial trisomy involving the region of synteny from chromosome 21 region contained in YAC 152F7, and new models, transgenic for the murine DYRK1A gene only.…”

Section: Discussionmentioning

confidence: 90%

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

Sebrié

Chabert

Ledru

et al. 2008

The Anatomical Record

View full text Add to dashboard Cite

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes-including DYRK1A, which encodes a serine threonine kinase involved in cell cycle controlhas been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2-7). Region-specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region-specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus-hypothalamus area (24%).

show abstract

Section: Discussionmentioning

confidence: 90%

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

Sebrié

Chabert

Ledru

et al. 2008

The Anatomical Record

View full text Add to dashboard Cite

show abstract

“…Cortical volume normalizes with increasing age into adulthood [97] and, depending on the report, may be smaller in later life [102]. Similarly, at PND 90, the lesioned mice showed robust increases in the width of all cortical layers, with different layers affected to a different extent in males and females [60].…”

Section: Discussionmentioning

confidence: 93%

“…This abnormal growth slows so that by late adolescence, brains are the same size as unaffected adults [3]. The findings of early postnatal brain overgrowth in autism followed by an abrupt cessation of growth in childhood, were recently confirmed in a meta-analysis of all eligible reports examining head circumference, magnetic resonance imaging (MRI), or postmortem brain weights from autism cases [97]. Initial MRI evaluation indicated that the increased brain volume in children with autism is the result of increased cerebral cortical gray matter and cerebral and cerebellar white matter [20,38].…”

Section: Introductionmentioning

confidence: 91%

Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

View full text Add to dashboard Cite

Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

show abstract

“…Structural neuroimaging studies of individuals with Autistic Disorder, who among individuals with ASD have the highest level of autistic symptomatology and the lowest level of adaptive functioning (Walker et al, 2004), have reported widespread abnormalities including agedependent increased brain volume (Aylward et al, 2002;Courchesne et al, 2001;Hazlett et al, 2005;Redcay and Courchesne, 2005;Sparks et al, 2002) reduced size of vermal lobules VI and VII (Ciesielski et al, 1997;Courchesne et al, 1994a;Courchesne et al, 1988;Hashimoto et al, 1995;Kaufmann et al, 2003), and reversed patterns of asymmetry (Herbert et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

et al. 2007

Self Cite

View full text Add to dashboard Cite

Rapid progress in our understanding of macrostructural abnormalities in autism spectrum disorders (ASD) has occurred in recent years. However, the relationship between the integrity of neural tissue and neural function has not been previously investigated. Single-voxel proton magnetic resonance spectroscopy and functional magnetic resonance imaging of an executive functioning task was obtained in 13 high functioning adolescents and adults with ASD and 13 agematched controls. The ASD group showed significant reductions in N-acetyl aspartate (NAA) in all brain regions combined and a specific reduction in left frontal cortex compared to controls. Regression analyses revealed a significant group interaction effect between frontal and cerebellar NAA. In addition, a significant positive semi-partial correlation between left frontal lobe NAA and frontal lobe functional activation was found in the ASD group. These findings suggest that widespread neuronal dysfunction is present in high functioning individuals with ASD. Hypothesized developmental links between frontal and cerebellar vermis neural abnormalities were supported, in that impaired neuronal functioning in the vermis was associated with impaired neuronal functioning in the frontal lobes in the ASD group. Furthermore, this study provided the first direct evidence of the relationship between abnormal functional activation in prefrontal cortex and neuronal dysfunction in ASD.

show abstract

When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports

Cited by 546 publications

References 58 publications

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

Modeling early cortical serotonergic deficits in autism

N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

Contact Info

Product

Resources

About