1Division of Neuropsychiatry, Department of Women's and Children's Health, Center of Neurodevelopmental Disorders at Karolinska Institutet, Karolinska Institutet, Stockholm, Sweden.
2Center for Psychiatry Research, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Mol Autism. 2019 Dec 31;11(1):1. doi: 10.1186/s13229-019-0309-x. eCollection 2020.
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.
In 75 twin pairs ( = 150, 62 females, 88 males) enriched for autism spectrum disorder ( = 32), and other neurodevelopmental disorders ( = 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.
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.
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.
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.
与男性相比，患有自闭症谱系障碍的女性表现出的受限和重复行为及兴趣较少且程度较轻。这种差异可能表明与自闭症症状领域相关的大脑网络存在特定于性别的改变，尤其是在皮质-纹状体和感觉整合网络中。本研究采用了一种经过良好控制的双胞胎设计，以检查与重复行为相关的大脑解剖结构的性别差异。
在 75 对双胞胎（=150 人，62 名女性，88 名男性）中，有自闭症谱系障碍（=32 人）和其他神经发育障碍（=32 人）的人群被富集，我们探讨了受限和重复行为及兴趣（通过自闭症诊断访谈修订版（C 领域）和社会反应量表-2（受限兴趣和重复行为子量表）来操作）与大脑皮质体积、皮质表面面积和厚度之间的关联。
同卵双胞胎对照分析显示，在女性中，RRBI 症状与右侧顶内沟的厚度增加和右侧眶额回的体积减少之间存在个体间关联，尽管男女之间的 RRBIs 平均数量没有差异。在 ASD 不一致对的子样本中，RRBI 与右侧眶额回、额上回和顶内沟的厚度增加有关，仅在女性中发现，而在男性中，RRBI 倾向于与双侧苍白球的体积增加有关。
然而，由于样本量小以及双胞胎内 RRBI 症状的差异小，本探索性研究的结果需要谨慎解释。
我们的研究结果表明，与 RRBIs 相关的额顶网络的结构改变主要发生在女性中，而纹状体网络在男性中受影响更大。这些结果支持了在自闭症症状的神经生物学中研究性别差异的重要性，并表明在女性和男性中，受限和重复行为及兴趣的潜在病因途径不同。
