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

进食障碍（ED）[神经性厌食症（AN），神经性贪食症（BN），暴食症（BED）和相关综合征]是常见的精神疾病，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，其发展受到环境，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（例如媒体曝光，理想化的瘦）和个性因素，但一系列其他因素要么未知，要么目前只能被视为相关因素。也有越来越广泛的接受ED作为大脑为基础的疾病共享神经生物学的重叠与焦虑症和成瘾。确定ED的真正风险因素，并了解它们如何促进疾病特定方面的发展，包括与奖励和惩罚，认知控制和情绪过程相关的行为，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功能失调性饮食行为的发展，我们将使用一个丰富的数据库，IMAGEN研究的青少年纵向队列。从四个欧洲国家招募了超过2000名参与者，包括英国，爱尔兰，德国和法国，并在14岁，16岁，19岁和23岁时进行随访，IMAGEN是最大和最全面的纵向基因x神经影像学队列。这项研究的青少年进行了神经影像学评估和广泛的评估，以监测健康和福祉，包括人格测量，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措施。还有与艾德症状、内化和外化行为以及物质使用相关的行为测量的广泛表征。为了证明在IMAGEN人群中观察到的任何差异也可适用于临床人群，我们将使用与最近一次IMAGEN随访（即约23岁）年龄相当、诊断为首次发作艾德（AN或BN/B艾德）的新兴成人样本补充IMAGEN样本。在接受艾德治疗之前，将以与IMAGEN受试者相似的方式对招募时未接受药物治疗的受试者进行评估。通过结合这两个样本，我们将能够在整个饮酒模式范围内识别功能失调饮食的多种相关性。对纵向IMAGEN数据集的重复测量的分析将使我们能够更好地确定哪些相关性在ED的发展中具有因果作用（那些在饮食失调症状出现之前发生的）。它们还将使我们能够描述可能的保护和/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，ED的领先专家和神经影像学，遗传学和发育精神病理学的科学领导者，形成了一个多学科团队，该团队非常适合提供必要的研究，以了解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.