Gender Differences in Autism Spectrum Disorders in a Population-Based Twin Sample, 2016-2019

This data collection is associated with a large population-based twin study of gender differences in autism. The data were collected from 2016-2019 from a sample population based in the UK. All participants were aged between 20-24 years of age at the time of data collection. The data deposited in this collection are taken from in-home assessments and accompanying questionnaires completed by the twins. The collection includes data from Autism Diagnostic Observation Schedule -2 assessments, the Social Responsiveness Scale (2nd edition) (a measure of autism traits), WASI IQ assessments, Strengths and Difficulties Questionnaire total domain scores (a measure of aspects of mental health) and the WHOQoL Bref (a measure of quality of life). Also included in the collection are demographic information for the participants including sex, age, zygosity and a grouping variable to indicate whether they were included in the study’s diagnosed, high trait or co-twin sample groups.<p>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.</p>

本数据集关联一项针对孤独症性别差异的大规模人群双生子研究。数据采集于2016至2019年，样本来自英国人群，所有参与者在数据采集时的年龄为20至24岁。本数据集收录的数据来自对双生子的居家评估及配套问卷，具体包括：孤独症诊断观察量表第二版（Autism Diagnostic Observation Schedule -2, ADOS-2）评估结果、社交反应量表第二版（Social Responsiveness Scale 2nd Edition, SRS-2，孤独症特质测评工具）、韦氏简式智力量表（WASI IQ）评估结果、长处与困难问卷总领域得分（心理健康维度测评工具）以及世界卫生组织生活质量简表（WHOQoL Bref，生活质量测评工具）。此外，数据集还包含参与者的人口学信息，包括性别、年龄、卵型分组，以及用于区分研究中确诊病例、高特质人群及双生子对照样本的分组变量。

本研究旨在基于人群双生子样本，探究孤独症谱系全维度的性别差异。孤独症谱系障碍（Autism Spectrum Disorder, ASD）是一种神经发育障碍，核心特征为社交行为与沟通困难，以及受限/重复的行为与兴趣模式。孤独症谱系障碍最显著的特征之一是极高的男性-女性患病比，该比例在谱系内存在波动，通常估算为4~5:1。男性孤独症谱系障碍患病率更高这一现象，被视为探究该病病因的重要线索，例如巴伦-科恩的“极端男性大脑”理论（Baron-Cohen, 2002），或是女性保护效应（Female Protective Effect, FPE；如Robinson等人, 2013）。不过，也有可能女性的孤独症谱系障碍诊断不足——这既可能源于男性化刻板印象，也可能源于女性的主动代偿行为。明确当前诊断流程是否遗漏了本应获得识别与干预的女性患者，具有重要的临床与科研意义。

本研究旨在直接解答以下核心问题：具有高孤独症特质的女性是否被当前诊断流程遗漏，或是通过代偿/适应机制无需获得诊断。为此，本研究将对四组参与者进行对比：符合孤独症谱系障碍诊断标准的女性与男性，以及虽孤独症特质评分较高但未达到诊断标准的女性与男性。四组参与者将完成一系列金标准诊断工具、认知任务、适应能力测评、生活质量测评、共病情况评估以及精神与身体健康测评。该研究设计不仅可对比不同性别群体的症状表现与认知特征，还可探究未获得诊断的高特质女性究竟是通过代偿实现了良好适应，还是“在沉默中承受痛苦”。明确我们为何、是否未能诊断女性的孤独症谱系障碍，对于厘清当前的性别差异究竟仅源于生物学因素，还是部分反映了以男性为中心的孤独症概念化、识别、评估或诊断流程存在缺陷，至关重要。

本研究是一项纵向孤独症谱系障碍双生子研究的一部分，嵌套于更大规模的双生子早期发展研究（Twins Early Development Study, TEDS）中。该设计可纳入非孤独症谱系障碍的双生子同胞，从而能够在更广泛的家庭层面探究性别差异，同时可专门检验女性保护效应假说——该假说认为，女性罹患孤独症谱系障碍需要比男性更高的病因学“负荷”。除女性保护效应外，本研究还将验证两项全新的假说：其一为“女性伪装效应”，即由于诊断流程以男性为中心，女性更难获得孤独症谱系障碍诊断；其二为“女性代偿效应”，即（在无智商缺陷/共病问题的前提下）女性可通过代偿更好地应对高孤独症特质，因此无需获得诊断。

本研究采用人群为基础的设计，并纳入全孤独症谱系人群，弥补了该领域此前研究的局限，例如可能存在的抽样偏差（因使用临床或志愿者登记样本）以及循环论证偏差（因仅纳入符合当前诊断标准的人群）。

本研究有望改变我们对孤独症谱系障碍的认知：当前公认的4~5:1患病比指导着研究设计与样本选择，而女性常被排除在研究之外。本研究将向科研、临床及利益相关群体阐明，该比例是否反映了识别、评估与诊断环节的偏差，这将对未来的研究产生深远影响。此外，本研究通过倾听并借鉴高孤独症特质女性/孤独症谱系障碍女性的经历，有望为该群体带来切实益处。本研究作为提升女性孤独症谱系障碍识别率的第一步，有望改善相关服务的靶向性，并重新平衡科学界与公众对孤独症谱系障碍的认知。