Gender Differences in Autism Spectrum Disorders in a Population-Based Twin Sample: testing three hypotheses for male preponderance.

这项拟议的研究旨在以双胞胎为样本，调查自闭症谱系的全部性别差异。自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交行为和沟通困难，行为和兴趣受到限制/重复。ASD最显著的特征之一是男性与女性的比例很高，这一比例在整个谱系中有所不同，但通常估计为4:5:1。男性中较高的ASD发病率被视为ASD病因的线索；例如Baron-Cohen的“极端男性大脑”理论（Baron-Cohen, 2002）或女性保护效应（FPE；例如Robinson et al., 2013）。然而，也有可能是由于男性的刻板印象或真正的补偿，ASD在女性中不太被认可。重要的是要知道目前的诊断方法是否遗漏了那些可以从识别和干预中受益的女性。这项提议的研究旨在直接解决这样一个问题，即具有高ASD特征的女性是否被诊断实践遗漏了，或者是在应对/补偿而不需要诊断。为此，拟议的研究将比较四个参与者组；符合ASD诊断标准的女性和男性，以及在ASD特征上得分较高但不符合诊断标准的女性和男性。四组将完成一系列黄金标准诊断工具、认知任务、应对措施、生活质量、合并症以及精神和身体健康。这种设计不仅可以比较不同性别的症状表现和认知特征，还可以检查没有诊断的高特征女性是在补偿还是在“沉默中受苦”。了解我们是否以及为什么不能诊断女性的ASD是至关重要的，以便澄清当前的性别差异是纯粹的生物学问题，还是部分反映了以男性为中心的ASD的概念化、识别、评估或诊断问题。拟议的研究是纵向ASD双胞胎研究的一部分，嵌套在更大的双胞胎早期发展研究（TEDS）中。该设计允许纳入非ASD的双胞胎，从而对性别进行更广泛的家庭探索，以及对FPE假设的具体检查，这表明导致女性ASD的病因学“负荷”比男性更大。与FPE一起，拟议的研究进一步测试了两个新的假设：“女性掩蔽效应”，即女性不太可能被诊断为ASD，因为她们被男性关注的诊断过程遗漏了；“女性补偿效应”，即女性不太可能被诊断为ASD，因为（在没有智商/共病问题的情况下）她们通过补偿更好地应对高ASD特征，因此不需要诊断。拟议研究的基于人群的设计和完整的ASD谱系的纳入，解决了该领域先前研究的局限性，例如可能的抽样偏差（由于使用诊所或志愿者登记的样本）和循环性（由于仅纳入符合当前诊断标准的样本）。这项提议的研究有可能改变我们对自闭症谱系障碍的看法；目前公认的4-5:1的比例用于研究设计和样本选择，女性经常被排除在研究之外。拟议的研究将告诉研究/临床/利益相关者社区，这个比例是否以及为什么会反映识别/评估/诊断的偏见，对未来的研究具有深远的意义。此外，该研究通过倾听和学习高特征/ASD女性的经历，对她们有潜在的好处。这项拟议的研究有可能提高女性对ASD的认识，作为针对服务和重新平衡科学和公众对ASD的看法的第一步。

The proposed research aims to investigate gender differences across the full range of the autism spectrum, in a population-based sample of twins. Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterised by difficulties in social behaviour and communication, with restricted/repetitive behaviours and interests. One of the most striking features of ASD is the high male to female ratio, which varies across the spectrum, but is usually estimated at 4-5:1. The higher rate of ASD in males has been seen as a clue to the etiology of ASD; e.g. Baron-Cohen's 'extreme male brain' theory (Baron-Cohen, 2002) or the Female Protective Effect (FPE; e.g. Robinson et al., 2013). However, it is also possible that ASD is less well recognised in females, either due to male-stereotypes or genuine compensation. It is important to know whether current diagnostic practices miss females who would benefit from identification and intervention. The proposed study aims to address directly the question of whether females with high ASD traits are being missed by diagnostic practices or are instead coping/compensating and do not need a diagnosis. To do this the proposed research will compare four participant groups; females and males who meet diagnostic criteria for ASD, and females and males who score highly for ASD traits, but who do not meet diagnostic criteria. A battery of gold-standard diagnostic tools, cognitive tasks, measures of coping, quality of life, co-morbidities and mental and physical health will be completed by the four groups. This design will allow not only comparison of symptom presentation and cognitive profiles across genders, but also examination of whether high trait females without a diagnosis are compensating or instead 'suffering in silence'. It is vital to understand whether, and why, we fail to diagnose ASD in females, in order to clarify whether the current gender disparity is purely biological or also a reflection, in part, of problems with a male-focused conceptualisation, recognition, assessment or diagnosis of ASD.The proposed study is part of a longitudinal ASD twin study, nested within the larger Twins Early Development Study (TEDS). This design allows for the inclusion of non ASD co-twins and thus a more family wide exploration of gender, as well as specific examination of the FPE hypothesis, which suggests that a greater etiological 'load' is needed to result in ASD in females than males. Along with the FPE the proposed study tests two further, novel hypotheses: the 'Female Masking Effect' whereby females are less likely to receive a diagnosis of ASD because they are missed by male-focused diagnostic processes, and the 'Female Compensatory Effect' whereby females are less likely to receive a diagnosis of ASD because (in the absence of IQ/co-morbid problems) they cope better with high ASD traits via compensation and therefore do not need a diagnosis. The population-based design of the proposed study and the inclusion of the full ASD spectrum, address previous limitations with research in this area, such as possible sampling bias (due to use of clinic or volunteer register samples) and circularity (due to inclusion of only those meeting current diagnostic criteria).The proposed study has the potential to change the way we think about ASD; currently the accepted ratio of 4-5:1 informs research design and sample selection, and females are often excluded from research. The proposed study will tell the research/clinical/stakeholder communities whether and why this ratio may reflect bias in recognition/assessment/diagnosis, with far reaching implications for future research. In addition, the study has potential benefits for females with high traits/ASD by listening to and learning from their experiences. The proposed study has the potential to improve recognition of ASD in females, as a first step to targeting services and rebalancing the scientific and public perception of ASD.