Establishing causal relationships between biopsychosocial predictors and correlates of eating disorders and their mediation by neural pathways

进食障碍[神经性厌食症(AN)、神经性暴食症(BN)、暴饮暴食障碍(BED)及相关综合征]是常见的精神障碍，在发达国家，影响高达15%的年轻女性和高达4%的年轻男性。这些疾病的原因是复杂的，它们的发展受到环境、心理和生物因素的影响，这些因素可能相互作用，产生不同临床表现的风险。虽然已知的风险因素包括社会文化影响(如媒体曝光、对苗条的理想化)和个性因素，但其他一系列因素要么未知，要么目前只能被认为是相关因素。人们也越来越广泛地接受EDS是一种基于大脑的疾病，与焦虑症和成瘾有神经生物学上的重叠。识别抑郁症的真正风险因素，并了解它们如何促进精神障碍的特定方面的发展，包括与奖惩相关的行为、认知控制和情绪过程，对于改进对抑郁症的预防和治疗至关重要。为了研究这一点并了解饮食功能障碍的行为是如何发展的，我们将使用IMAGEN研究中收集的大量基于人群的纵向青少年队列来收集丰富的数据库。IMAGEN从包括英国、爱尔兰、德国和法国在内的四个欧洲国家招募了2000多名参与者，并在14、16、19和23岁进行了跟踪调查，是规模最大、特征最全面的纵向基因x神经成像队列。这项研究的青少年接受了神经成像评估和广泛的评估，以监测健康和幸福感，包括人格测量、社会决定因素、产前和产后生活事件问卷、神经心理和生物测量。还广泛描述了与勃起功能障碍症状、内化和外化行为和物质使用有关的行为衡量标准。为了证明在IMAGEN人群中观察到的任何差异也适用于临床人群，我们将用与最近一次IMAGEN随访(即~23岁)相当的年龄的新兴成年人样本来补充IMAGEN样本，这些样本被诊断为首发ED(AN或BN/BED)。在接受ED治疗之前，这些人在招募时没有接受药物治疗，将以类似于IMAGEN参与者的方式进行评估。通过将这两个样本结合起来，我们将能够在整个饮酒模式范围内识别出与饮食失调有关的多种因素。对纵向IMAGEN数据集重复测量的分析将使我们能够更好地确定哪些相关性在EDS(那些发生在进食障碍症状出现之前的)的发展中具有因果作用。它们还将使我们能够确定可能的保护性和/或额外的风险因素，包括环境和生物因素。对于这项研究，我们汇集了独特的资源、EDS领域的一位领先专家以及神经成像、遗传学和发展精神病理学方面的科学领导者，组成了一个多学科团队，该团队处于有利地位，能够提供必要的研究，以了解EDS的潜在机制和异质性，并为未来的预防和治疗策略提供信息。

The eating disorders (EDs) [anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and related syndromes] are common psychiatric disorders that affect up to 15% of young women and up to 4% of young men in developed countries. The cause of these disorders is complex and their development influenced by environmental, psychological and biological factors that may interact to create a risk for different clinical presentations of the disorder. While known risk factors include sociocultural influences (e.g. media exposure, idealisation of thinness) and personality factors, a range of other factors are either unknown or can currently only be considered as correlates. There is also the increasingly broad acceptance of EDs as being brain-based disorders sharing neurobiological overlaps with anxiety disorders and addictions. Identifying true risk factors for EDs and understanding how they contribute to the development of the specific aspects of the disorders, including behaviours related to reward and punishment, cognitive control and emotional processes, will be crucial for improving prevention and treatment of EDs.To investigate this and understand how behaviours of dysfunctional eating develop, we will use a rich database collected a large population-based, longitudinal cohort of adolescents of the IMAGEN study. With over n=2000 participants recruited from four European countries, including the UK, Ireland, Germany and France, and followed-up at ages 14, 16, 19 and 23, IMAGEN is the largest and most comprehensively characterized longitudinal gene x neuroimaging cohort. The adolescents of this study underwent neuroimaging assessments and extensive assessments to monitor health and wellbeing, including personality measures, social determinants, and pre- and post-natal life-events questionnaires, neuropsychological and biological measures. There is also an extensive characterisation of behavioural measures related to ED symptoms, internalising and externalising behaviours and substance use. To demonstrate that any differences observed in the IMAGEN population can also apply to a clinical population, we will complement the IMAGEN sample with a sample of emerging adults, of comparable age to the most recent IMAGEN follow-up (i.e. ~ 23 years-old), diagnosed with a first episode ED (AN or BN/BED). Before undergoing treatment for their ED, those individuals, unmedicated at the time of recruitment, will be assessed in a similar way as the IMAGEN participants. By combining these two samples we will be in a position to identify multiple correlates of dysfunctional eating across the full spectrum of drinking patterns. The analyses of the repeated measures of the longitudinal IMAGEN dataset, will allow us to better establish which correlates have a causal role in the development of EDs (those occurring before appearance of eating disorder symptoms). They will also enable us to characterising possible protective and/or additional risk factors, both environmental and biological. For this research, we have brought together unique resources, a leading expert in EDs and scientific leaders in neuroimaging, genetics and developmental psychopathology to form a multi-disciplinary team, which is excellently positioned to deliver the research necessary to understand the underlying mechanisms and heterogeneity of EDs and inform future prevention and treatment strategies.