Brain Volume In Autism Research Articles

Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis

Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use.

Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation

BackgroundPatients with autism have been often reported to have a smaller corpus callosum (CC) than control subjects. MethodsWe conducted a meta-analysis of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging Data Exchange project, and performed computer simulations to study the effect of different analysis strategies. ResultsOur meta-analysis suggested a group difference in CC size; however, the studies were heavily underpowered (20% power to detect Cohen’s d = .3). In contrast, we did not observe significant differences in the Autism Brain Imaging Data Exchange cohort, despite having achieved 99% power. However, we observed that CC scaled nonlinearly with brain volume (BV): large brains had a proportionally smaller CC. Our simulations showed that because of this nonlinearity, CC normalization could not control for eventual BV differences, but using BV as a covariate in a linear model would. We also observed a weaker correlation of IQ and BV in cases compared with control subjects. Our simulations showed that matching populations by IQ could then induce artifactual BV differences. ConclusionsThe lack of statistical power in the previous literature prevents us from establishing the reality of the claims of a smaller CC in autism, and our own analyses did not find any. However, the nonlinear relationship between CC and BV and the different correlation between BV and IQ in cases and control subjects may induce artifactual differences. Overall, our results highlight the necessity for open data sharing to provide a more solid ground for the discovery of neuroimaging biomarkers within the context of the wide human neuroanatomical diversity.

The neuroanatomy of the autistic phenotype

The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X syndrome [FXS]). We investigated brain volume in 37 participants, using the fully automated Civet pipeline anatomical magnetic resonance imaging. 3 groups with intellectual deficiency: autism (AUT); its most associated FXS; and its most opposite Williams syndrome (WS) were compared with each other and with normal controls (NC). We report increased total and regional gray and white matter brain volume in AUT and FXS relative to WS and NC. These findings are discussed in light of the possibilities leading for the enlarged brain volume in children with the AUT phenotype. We speculate that this excess suggests reduced regression of neuronal processes “pruning” in cortical and subcortical regions in AUT/FXS, which may be due to a mutation in specific genes involved in pruning and/or a lack of socio-emotional environmental experience during a critical developmental period.

Advances in autism neuroimaging research for the clinician and geneticist

This review focuses on recent advances in the in vivo study of the whole brain in idiopathic autism. The brain is abnormally large in some but not all children with autism during post-natal development. Age-related changes in brain volume in autism are complex and appear to be abnormal from infancy into adulthood. Diffuse differences in total and regional gray and white matter volumes are found. The volumetric abnormalities appear to follow anomalous, complex, and non-uniform developmental curves. Diffuse abnormalities of brain chemical concentrations, neural network anatomy, brain lateralization, intra- and inter-hemispheric morphologic and functional connectivity, and serotonin synthesis capacity are also found. Abnormalities of head growth are first apparent during infancy. Abnormalities of total brain volume, gray and white matter volumes, brain chemistry, serotonin synthesis, and brain electrophysiology are evident by early childhood. Currently, no method of brain imaging helps with diagnosis or treatment of idiopathic autism, but ongoing research aims to unravel the heterogeneity of autism and may provide future diagnostic tools that inform treatment.

Evidence of Toxicity, Oxidative Stress, and Neuronal Insult in Autism

According to the Autism Society of America, autism is now considered to be an epidemic. The increase in the rate of autism revealed by epidemiological studies and government reports implicates the importance of external or environmental factors that may be changing. This article discusses the evidence for the case that some children with autism may become autistic from neuronal cell death or brain damage sometime after birth as result of insult; and addresses the hypotheses that toxicity and oxidative stress may be a cause of neuronal insult in autism. The article first describes the Purkinje cell loss found in autism, Purkinje cell physiology and vulnerability, and the evidence for postnatal cell loss. Second, the article describes the increased brain volume in autism and how it may be related to the Purkinje cell loss. Third, the evidence for toxicity and oxidative stress is covered and the possible involvement of glutathione is discussed. Finally, the article discusses what may be happening over the course of development and the multiple factors that may interplay and make these children more vulnerable to toxicity, oxidative stress, and neuronal insult.

Brain anatomy in non-affected parents of autistic probands: a MRI study

Autism is a neurodevelopmental disorder with an estimated genetic origin of 90%. Previous studies have reported an increase in brain volume of approximately 5% in autistic subjects, especially in children. If this increase in brain volume is genetically determined, biological parents of autistic probands might be expected to show brain enlargement, or at least intracranial enlargement, as well. Identifying structural brain abnormalities under genetic control is of particular importance as these could represent endophenotypes of autism. Using quantitative anatomic brain magnetic resonance imaging, volumes of intracranial, total brain, frontal, parietal, temporal and occipital lobe, cerebral and cortical gray and white matter, cerebellum, lateral ventricle, and third ventricle were measured in biological, non-affected parents of autistic probands (19 couples) and in healthy, closely matched control subjects (20 couples). No significant differences were found between the parents of the autistic probands and healthy control couples in any of the brain volumes. Adding gender as a factor in a second analysis did not reveal a significant interaction effect of gender by group. The present sample of biological, non-affected parents of autistic probands did not show brain enlargements. As the intracranium is not enlarged, it is unlikely that the brain volumes of the parents of autistic probands have originally been enlarged and have been normalized. Thus, increased brain volume in autism might be caused by the interaction of paternal and maternal genes, possibly with an additional effect of environmental factors, or increased brain volumes might reflect phenotypes of autism.

Review on structural neuroimaging findings in autism.

Autism is now widely viewed as a neurodevelopmental disorder, although the underlying biological causes remain to be established. In this review, we examine the literature in magnetic resonance imaging (MRI) as applied to autism, discuss the findings that have emerged, and give directions for potential future research. To date, structural MRI results are inconsistent, partly due to the heterogeneity of the disorder itself, and partly due to the different composition and the varied degree of matching of the studied groups. However, recent studies have begun to elucidate the underlying neuroanatomical abnormalities and brain-behavior relationships in autism, with the most consistent finding being increased brain volume in autism. Future large-scale longitudinal structural imaging studies, starting at very young ages, investigating homogeneous groups of patients and extensively matched control groups, and making use of (combinations of) newer and more sophisticated techniques, hold a great promise to further elucidate the enigma of autism.

Brain volume in autism.

Increased brain size has been observed in individuals with autism with a wide range of cognitive functioning. The purpose of this investigation was to obtain measurements of the brain volume in a sample of nonmentally retarded autistic individuals. Magnetic resonance imaging scans from 16 nonmentally retarded individuals with autism and 19 male volunteer comparison subjects were obtained and the following structures were measured: third, fourth, and lateral ventricles and intracranial and cerebral volumes. Mean cerebral and third ventricle volumes in the autistic subjects were significantly greater than in the controls when adjusted for intracranial volume. No other significant results were found. Our finding of increased brain volume in autism is consistent with previous reports in the literature. Additional longitudinal neuroimaging and, more importantly, neuropathologic studies are warranted to provide a better understanding of the complexities underlying increased brain size in autism.

Brain Volume in Autism

Brain Volume in Autism

Regional Brain Enlargement in Autism: A Magnetic Resonance Imaging Study

To determine whether increased brain volume in autism, suggested in previous studies, is the result of general or regional brain size differences and to study the effect of gender on brain size and pattern of enlargement. Total brain volume and cerebral cortical lobe volumes were examined in 35 autistic and 36 comparison subjects using magnetic resonance imaging and an automated method of brain volume measurement. After controlling for height and nonverbal IQ, the authors detected a significant diagnosis x gender effect (F = 7.4; p = .009) for total brain volume. A repeated-measures analysis of variance indicated that the pattern of enlargement (brain region x diagnosis) in autistic subjects differed from that in controls (F = 4.88; p = .0004). Subsequent sex-specific analysis revealed significantly increased total brain volume in autistic males but not females. Analysis of lobe sizes showed significant enlargement in autistic subjects in temporal, parietal, and occipital, but not frontal lobes. These results suggest that brain size is increased in autism and that differences are not generalized but appear to be the result of a pattern of enlargement with increases in the size of specific cortical lobes.