Abstract

BackgroundAutism spectrum disorder (ASD) is diagnosed much less often in females than males. Emerging behavioral accounts suggest that the clinical presentation of autism is different in females and males, yet research examining sex differences in core symptoms of autism in affected children has been limited. Additionally, to date, there have been no systematic attempts to characterize neuroanatomical differences underlying the distinct behavioral profiles observed in girls and boys with ASD. This is in part because extant ASD studies have included a small number of girls.MethodsLeveraging the National Database for Autism Research (NDAR), we first analyzed symptom severity in a large sample consisting of 128 ASD girls and 614 age- and IQ-matched ASD boys. We then examined symptom severity and structural imaging data using novel multivariate pattern analysis in a well-matched group of 25 ASD girls, 25 ASD boys, 19 typically developing (TD) girls, and 19 TD boys, obtained from the Autism Brain Imaging Data Exchange (ABIDE).ResultsIn both the NDAR and ABIDE datasets, girls, compared to boys, with ASD showed less severe repetitive/restricted behaviors (RRBs) and comparable deficits in the social and communication domains. In the ABIDE imaging dataset, gray matter (GM) patterns in the motor cortex, supplementary motor area (SMA), cerebellum, fusiform gyrus, and amygdala accurately discriminated girls and boys with ASD. This sex difference pattern was specific to ASD as the GM in these brain regions did not discriminate TD girls and boys. Moreover, GM in the motor cortex, SMA, and crus 1 subdivision of the cerebellum was correlated with RRB in girls whereas GM in the right putamen—the region that discriminated TD girls and boys—was correlated with RRB in boys.ConclusionsWe found robust evidence for reduced levels of RRB in girls, compared to boys, with ASD, providing the strongest evidence to date for sex differences in a core phenotypic feature of childhood ASD. Sex differences in brain morphometry are prominent in the motor system and in areas that comprise the “social brain.” Notably, RRB severity is associated with sex differences in GM morphometry in distinct motor regions. Our findings provide novel insights into the neurobiology of sex differences in childhood autism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0042-z) contains supplementary material, which is available to authorized users.

Highlights

  • Autism spectrum disorder (ASD) is diagnosed much less often in females than males

  • Analysis of neuroanatomical data from the Autism Brain Imaging Data Exchange (ABIDE) dataset revealed, for the first time, that girls and boys with ASD differ in the organization of cortical and subcortical motor systems and that restricted behaviors (RRBs) severity is associated with sex differences in gray matter (GM) morphometry in distinct motor systems

  • Based on brain regions that showed sex differences in ASD, we found that the GM morphometry in the motor cortex, supplementary motor area (SMA), and cerebellum was correlated with scores on the RRB domain of the ADI-R

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Summary

Introduction

Autism spectrum disorder (ASD) is diagnosed much less often in females than males. Emerging behavioral accounts suggest that the clinical presentation of autism is different in females and males, yet research examining sex differences in core symptoms of autism in affected children has been limited. To date, there have been no systematic attempts to characterize neuroanatomical differences underlying the distinct behavioral profiles observed in girls and boys with ASD. This is in part because extant ASD studies have included a small number of girls. Apart from autism symptomatology, little is known about sex differences in brain organization in childhood ASD This is in part because extant brain imaging studies have almost exclusively focused on boys or mixed gender samples involving a small number of girls, with a recent meta-analysis suggesting a large male bias of 8:1 in structural neuroimaging studies of autism [9]. This knowledge is critical for understanding the etiology of this heterogeneous disorder and for understanding neuroprotective factors in girls [10]

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