title: The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study.
abstract: BACKGROUND
  Genetic, 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  For 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.
  
  
  CONCLUSIONS
  Despite 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.
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Pisa Division, Largo B. Pontecorvo 3, 56127 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Retico
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Pisa Division, Largo B. Pontecorvo 3, 56127 Pisa, Italy ; University of Pisa, Department of Physics, Largo B. Pontecorvo 3, 56127 Pisa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Giuliano
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tancredi
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cosenza
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Apicella
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Narzisi
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Biagi
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Tosetti
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy ; University of Pisa, Department of Clinical and Experimental Medicine, Via Savi 10, 56126 Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Muratori
authors.affiliation: IRCCS Stella Maris Foundation, viale del Tirreno 331, 56018 Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Calderoni
mesh_terms: D019540:Area Under Curve; D000067877:Autism Spectrum Disorder / Q000473:pathology*; D002555:Cerebrospinal Fluid; D002648:Child; D002675:Child, Preschool; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007223:Infant; D007360:Intelligence; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009929:Organ Size; D010641:Phenotype; D012107:Research Design; D012720:Severity of Illness Index; D012727:Sex Characteristics; D060388:Support Vector Machine; D066127:White Matter / Q000473:pathology
keywords: Autism spectrum disorders; Gender differences; Structural MRI; Support vector machine; Young children