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. 2019 Dec 31;11(1):1.
doi: 10.1186/s13229-019-0309-x. eCollection 2020.

Sex differences in brain structure: a twin study on restricted and repetitive behaviors in twin pairs with and without autism

Annelies Van't Westeinde #  1   2 , Élodie Cauvet #  1   2 , Roberto Toro  3   4   5 , Ralf Kuja-Halkola  6 , Janina Neufeld  1   2 , Katell Mevel  7 , Sven Bölte  1   2   8   9
Affiliations

Sex differences in brain structure: a twin study on restricted and repetitive behaviors in twin pairs with and without autism

Annelies Van't Westeinde et al. Mol Autism. .

Abstract

Background: Females with autism spectrum disorder have been reported to exhibit fewer and less severe restricted and repetitive behaviors and interests compared to males. This difference might indicate sex-specific alterations of brain networks involved in autism symptom domains, especially within cortico-striatal and sensory integration networks. This study used a well-controlled twin design to examine sex differences in brain anatomy in relation to repetitive behaviors.

Methods: In 75 twin pairs (n = 150, 62 females, 88 males) enriched for autism spectrum disorder (n = 32), and other neurodevelopmental disorders (n = 32), we explored the association of restricted and repetitive behaviors and interests-operationalized by the Autism Diagnostic Interview-Revised (C domain) and the Social Responsiveness Scale-2 (Restricted Interests and Repetitive Behavior subscale)-with cortical volume, surface area and thickness of neocortical, sub-cortical, and cerebellar networks.

Results: Co-twin control analyses revealed within-pair associations between RRBI symptoms and increased thickness of the right intraparietal sulcus and reduced volume of the right orbital gyrus in females only, even though the mean number of RRBIs did not differ between the sexes. In a sub-sample of ASD-discordant pairs, increased thickness in association with RRBIs was found exclusively in females in the orbitofrontal regions, superior frontal gyrus, and intraparietal sulcus, while in males RRBIs tended to be associated with increased volume of the bilateral pallidum.

Limitations: However, due to a small sample size and the small difference in RRBI symptoms within pairs, the results of this exploratory study need to be interpreted with caution.

Conclusions: Our findings suggest that structural alterations of fronto-parietal networks in association with RRBIs are found mostly in females, while striatal networks are more affected in males. These results endorse the importance of investigating sex differences in the neurobiology of autism symptoms, and indicate different etiological pathways underlying restricted and repetitive behaviors and interests in females and males.

Keywords: Autism; Neuroanatomy; Repetitive behaviors; Sex differences; Twins.

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Conflict of interest statement

Competing interestsSven Bölte declares no direct conflict of interest related to this article. He discloses that he has in the last 5 years acted as an author, consultant, or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Kompetento, Expo Medica, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Brain region associated with restricted and repetitive behaviors and interests in females. Within-pair association between ADI-R C and brain structure. The area that was significantly associated with RRBIs is displayed blue: increased thickness of the right intraparietal sulcus in females. Areas not significantly associated with RRBIs, but included in our regions of interest, are displayed in soft green
See this image and copyright information in PMC

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