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

患有自闭症谱系障碍的男性和女性青春期大脑解剖结构和连接性的发展

• 批准号: 271513085
• 负责人: Professorin Dr. Christine Ecker, Ph.D.
• 金额: --
• 依托单位: Brain Imaging Center (BIC)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/271513085?language=en
• 关键词: Development; Brain; Anatomy; Connectivity; Males

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.

自闭症谱系障碍(ASD)是一种终生神经发育障碍，其特征是缺乏社会互惠、社会沟通和重复/刻板印象行为。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，研究都同意ASD伴随着大脑成熟和大脑连接改变的非典型轨迹。儿童早期的非典型神经发育轨迹在ASD中有很好的特征。然而，调节ASD青春期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，大脑从青春期到成年早期都在继续成熟，特别是在晚期成熟的额叶和颞叶系统中，这两个系统在自闭症患者通常受损的社会和情绪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课程设定的时期。因此，对青春期早期ASD的神经病理的洞察可以为青春期晚期和成年期早期临床结局的发展提供重要的预测信息。因此，这项研究的第一个主要目的是建立ASD儿童后期到成年早期大脑成熟的神经病理机制，并开发能够预测青春期晚期临床结果的青春期早期生物标志物。初步证据还表明，ASD作为生物性别的一种功能表现不同，ASD男性和女性在各自的行为和神经病理表型方面也不同。然而，目前尚不清楚青春期是否对男性和女性ASD患者的神经病理和症状特征产生不同的影响，与典型的神经对照组相比。因此，这项研究的第二个目的是确定青春期ASD的皮质病理和神经发育轨迹在多大程度上受到生物性别的调节，并检查青春期可能调节成年早期自闭症症状严重程度的潜在神经保护因素。我们拟议的工作结果将为青春期ASD的神经病理学提供重要的新见解，并阐明神经生物学和临床ASD表型的性别差异，这可能为未来青春期ASD的诊断和治疗提供参考。然而，最重要的是，我们的研究将对ASD早期体内生物标记物的开发做出重大贡献，这些标记物可以用于稍后预测临床结果，从而增加正在进行的将研究结果转化为临床实践的全球研究努力。