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

饮食失调（EDs）[神经性厌食症（AN），神经性贪食症（BN），暴食症（BED）及相关综合症]是常见的精神疾病，影响着发达国家高达15%的年轻女性和高达4%的年轻男性。这些疾病的病因是复杂的，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，造成疾病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、对瘦的理想化）和个性因素，但一系列其他因素要么是未知的，要么目前只能被认为是相关的。人们也越来越广泛地接受，ed是一种基于大脑的疾病，与焦虑症和成瘾症有着神经生物学上的重叠。识别ed的真正危险因素，并了解它们如何促进障碍的特定方面的发展，包括与奖励和惩罚有关的行为，认知控制和情绪过程，对于改善ed的预防和治疗至关重要。为了调查这一点并了解饮食功能失调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的丰富数据库。IMAGEN从英国、爱尔兰、德国和法国等四个欧洲国家招募了超过2000名参与者，随访年龄分别为14岁、16岁、19岁和23岁。IMAGEN是规模最大、特征最全面的纵向基因x神经影像学队列。本研究的青少年接受了神经影像学评估和广泛的评估，以监测健康和福祉，包括个性测量、社会决定因素、产前和产后生活事件问卷调查、神经心理学和生物学测量。还有与ED症状、内化和外化行为以及药物使用相关的行为测量的广泛特征。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IMAGEN随访年龄相当（即~ 23岁）、诊断为首发ED （AN或BN/BED）的新生成人样本补充IMAGEN样本。在接受ED治疗之前，这些在招募时未接受药物治疗的个体将以与IMAGEN参与者相似的方式进行评估。通过结合这两个样本，我们将能够在整个饮酒模式的范围内确定饮食功能失调的多种相关因素。对纵向IMAGEN数据集的重复测量进行分析，将使我们能够更好地确定哪些相关因素在EDs（在饮食失调症状出现之前发生的疾病）的发展中具有因果作用。它们还将使我们能够描述可能的保护和/或额外的环境和生物风险因素。在这项研究中，我们汇集了独特的资源，一位领先的ed专家和神经影像学、遗传学和发育精神病理学的科学领袖，组成了一个多学科的团队，这是一个很好的定位，可以提供必要的研究，了解ed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.