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调查以人口为基础的双胞胎样本中，自闭症谱系的所有范围内的性别差异。自闭症谱系障碍(ASD)是一种以社交行为和沟通困难为特征的神经发育状况，具有受限/重复的行为和兴趣。ASD最显著的特征之一是高的男性和女性比例，这一比例在光谱中有所不同，但通常估计为4-5：1。男性ASD的较高比率被视为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等人，2013)。然而，也可能是由于男性的刻板印象或真正的补偿，自闭症在女性中不太被认可。重要的是要知道目前的诊断实践是否遗漏了将从识别和干预中受益的女性。这项拟议的研究旨在直接解决以下问题：具有高度自闭症特征的女性是被诊断实践遗漏了，还是正在应对/补偿而不需要诊断。为了做到这一点，拟议的研究将比较四个参与者群体：符合ASD诊断标准的女性和男性，以及ASD特征得分高但不符合诊断标准的女性和男性。这四个小组将完成一系列黄金标准的诊断工具、认知任务、应对措施、生活质量、合并症以及心理和身体健康。这一设计不仅可以比较不同性别的症状表现和认知特征，还可以检查没有确诊的高特质女性是在补偿还是在默默忍受。了解我们是否以及为什么未能在女性中诊断ASD是至关重要的，以便澄清目前的性别差异是纯粹的生物学上的，还是部分反映了以男性为重点的ASD概念化、识别、评估或诊断方面的问题。拟议的研究是ASD纵向双胞胎研究的一部分，该研究嵌套在更大的双胞胎早期发展研究(TEDS)中。这一设计允许包括非ASD同卵双胞胎，因此对性别进行了更广泛的家庭范围的探索，并对FPE假说进行了具体检查，该假说表明，导致女性ASD的病因‘负荷’比男性更大。除了FPE，这项拟议的研究还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；以及“女性代偿效应”，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纳入完整的ASD谱，解决了这一领域先前研究的局限性，例如可能的抽样偏差(由于使用临床或志愿者登记的样本)和循环性(由于只纳入那些符合当前诊断标准的样本)。拟议的研究有可能改变我们对ASD的看法；目前公认的4-5：1的比率为研究设计和样本选择提供信息，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，这一比率是否以及为什么可能反映认识/评估/诊断方面的偏见，对未来的研究具有深远的影响。此外，这项研究通过倾听和学习她们的经历，对具有高特质/自闭症的女性有潜在的好处。这项拟议的研究有可能提高女性对自闭症的认识，作为确定服务目标和重新平衡科学和公众对自闭症认知的第一步。

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.