The Development of Brain Anatomy and Connectivity in Males and Females with Autism Spectrum Disorder during Adolescence

自闭症谱系障碍（ASD）是一种终身神经发育障碍，其特征是社交互惠，社交沟通和重复/刻板行为的缺陷。虽然ASD患者之间存在相当大的异质性，无论是病因还是表型，但研究一致认为ASD伴随着大脑成熟和大脑连接改变的非典型轨迹。在ASD中，儿童早期的非典型神经发育轨迹具有很好的特征。然而，在ASD青少年期间介导大脑成熟的神经生物学机制仍然知之甚少。现在人们普遍认为，大脑在青春期持续成熟，直到成年早期，特别是在成熟较晚的额叶和颞叶系统中，这些系统在ASD中通常受损的社会和情感行为的发展中起着至关重要的作用。青春期也是成人神经发育和行为的时期。因此，对青少年早期ASD的神经病理学的了解可以为青少年晚期和成年早期的临床结果的发展提供重要的预测信息。因此，拟议研究的第一个主要目的是建立ASD中从儿童晚期到成年早期介导大脑成熟的神经病理学机制，并开发可以预测青春期后期临床结果的青春期早期生物标志物。初步证据还表明，自闭症谱系障碍因生物性别而表现不同，并且患有自闭症谱系障碍的男性和女性在各自的行为和神经病理表型方面也有所不同。然而，目前尚不清楚青春期是否对ASD男性和女性的神经病理学和症状特征产生差异性影响，与神经典型对照组相比。因此，本研究的第二个目的是建立在何种程度上的皮质病理学和神经发育轨迹的ASD在青春期调制的生物性别，并检查潜在的神经保护因素，在青春期，可以调节自闭症症状的严重程度在成年早期。我们所提出的工作的结果将提供重要的新见解，在青春期ASD的神经病理学，并阐明神经生物学和临床ASD表型的性别差异，这可能会告知未来的方法来诊断和治疗ASD在青春期。然而，最重要的是，我们的研究将为ASD早期体内生物标志物的开发做出重大贡献，这些生物标志物可用于以后的临床结果预测，从而增加了正在进行的全球研究工作，将研究结果转化为临床实践。

Autism Spectrum Disorder (ASD) is a life-long neurodevelopmental disorder characterized by deficits in social reciprocity, social communication, and repetitive/stereotypic behaviours. While there is considerable heterogeneity among individuals with ASD, both causative and phenotypic, research agrees that ASD is accompanied by an atypical trajectory of brain maturation and altered brain connectivity. The atypical neurodevelopmental trajectory during early childhood is well characterized in ASD. However, the neurobiological mechanisms that mediate brain maturation during adolescence in ASD remain poorly understood. It is now widely accepted that the brain continues to mature through adolescence until early adulthood, particularly in late maturing frontal and temporal lobe systems, which play a crucial role in the development of the social and emotional behaviors typically impaired in ASD. Adolescence is also a time where the course for adult neurodevelopment and behavior is set. Insights into the respective neuropathology of ASD during early adolescence could therefore provide important predictive information for the development of clinical outcomes during late adolescence and early adulthood. The first main aim of the proposed research is thus to establish the neuropathological mechanisms mediating brain maturation from late childhood to early adulthood in ASD, and to develop early adolescence biomarkers that could predict clinical outcomes during late adolescence. Preliminary evidence also suggests that ASD manifests differently as a function of biological sex, and that males and females with ASD differ in terms of their respective behavioural and neuropathological phenotypes. However, it is currently unknown whether adolescence exerts a differential effect on the neuropathology and symptom profiles in males and females with ASD, compared to neurotypical controls. The second aim of the study is thus to establish the extend to which the cortical pathology and neurodevelopmental trajectory of ASD during adolescence is modulated by biological sex, and to examine potential neuroprotective factors in adolescence that could modulate the severity of autistic symptoms in early adulthood. The outcomes of our proposed work will provide important novel insights into the neuropathology of ASD during adolescence, and elucidate gender-differences in the neurobiological and clinical ASD phenotype, which may inform future approaches to diagnosing and treating ASD during adolescence. Most importantly, however, our research will significantly contribute to the development of early in vivo biomarkers for ASD that could be utilized in the prediction of clinical outcomes later on, and thus adds to ongoing global research efforts towards translating research findings into clinical practice.