The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study

Abstract

BackgroundGenetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings.MethodsA total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2–7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism.ResultsFor both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area –BA– 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus—BA 19—and right superior temporal gyrus—BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD.ConclusionsDespite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0067-3) contains supplementary material, which is available to authorized users.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span

“…Increasingly, the behavioral characteristics and functionalities of the “male brain” have been cited as risk factors and characteristics of autism spectrum disorders (Baron-Cohen et al, 2005). Imaging studies separately comparing boys and girls with autism to those without autism, are now being conducted, and suggest sex-specific structural network disruptions underpinning the neurobiology of the disorder (Lai et al, 2013, Retico et al, 2016). …”

Neurobiological support to the diagnosis of ADHD in stimulant‐naïve adults: pattern recognition analyses of MRI data

“…However, this possibility has to be raised with great caution; we were not able to also conduct female‐only analyses because of limited sample size, and we cannot therefore rule out the alternative explanation that the greater AUC values in the male‐only analyses simply reflected the use of a gender‐homogeneous sample. Nevertheless, it is interesting to note that one recent ML‐based structural MRI study of prototypical neurodevelopmental autism spectrum disorders showed a similar degree of improvement on discrimination performance in male‐only SVM analyses, but not in analyses restricted to a female subgroup of the same size . Thus better, classification results in male‐only SVM analyses carried out with disorders such as autism or childhood‐onset ADHD may not simply be because of the use of homogeneous groups in regard to gender.…”

Sex differences along the Autism Continuum: A twin study of brain structure

“…Further, the structural alterations observed in females appeared in different brain regions as compared to males, in particular reduced volume of temporal and frontal cortices, which has been observed in adults (Craig et al 2007;Ecker et al 2017), as well as young children in a reversed pattern (Retico et al 2016). Indeed, little overlap in brain structure alterations associated with ASD might exist between sexes (Lai et al 2013).…”

“…For example, decreased cortical thickness is observed in females with ASD, as opposed to increased cortical thickness in males with ASD, in the inferior and middle temporal lobes (Ecker et al 2017). Therefore, both quantitative and qualitative neuroanatomical differences in association with autistic traits might be expected between males and females, as previous research indeed indicates (Bloss and Courchesne 2007;Craig et al 2007;Schumann et al 2010;Lai et al 2013;Schaer et al 2015;Retico et al 2016). Using a withinpair design provides valuable insights into neuroanatomical sex differences by testing if autistic trait differences within female twin pairs are associated with more structural brain differences compared to male twin pairs.…”