The Triple A study (Adolescents with Anorexia and Autism): A search for biomarkers

神经性厌食症是一种复杂的进食障碍，具有较高的生理和心理风险，是精神障碍中死亡率最高的疾病。对临床医生和研究人员来说，治疗耐药性是一个巨大的挑战，因为大约50%被诊断为AN的人对治疗没有反应，并继续发展为更严重和更慢性的疾病。一项探索AN患者的思维方式和情感特征的研究表明，AN患者和从未患过饮食紊乱的人在思维过程中存在差异。这些问题包括思维方式僵化、拘泥于细节，以及难以识别和表达情绪以及与他人互动等社交功能。脑成像研究也强调了AN患者在这些过程中大脑功能的不同模式。这些困难被认为是导致这种障碍发展和维持的一个主要因素。这些特征也定义了自闭症谱系障碍(ASD)的症状，这导致了对AN和ASD之间重叠的研究。尽管ASD和AN的性别比例相反(ASD在男性中更常见，在女性中更常见)，但最近的研究结果表明，患有严重和慢性AN的成年女性中，有一部分自闭症症状水平较高。这种升高的ASD特征也与较差的治疗结果有关。在疾病的早期阶段，几乎没有工作关注这种疾病特征，迫切需要研究患有ASD的年轻人在他们第一次出现这种疾病时的认知和神经生物学特征，同时考虑ASD症状在他们康复中的潜在作用。对思维和情绪处理过程中大脑活动的研究主要是在成年人和人群中进行的，还需要进一步的研究来探索患有AN的年轻人的大脑激活是否存在类似的异常和差异，以及随着疾病的进展或体重恢复，这种异常和差异可能会如何变化。探索年轻人在首次出现症状时、疾病期间和康复后对大脑的影响将有助于确定风险和维持因素，并有助于预测治疗结果。总体而言，这项工作可能有助于开发针对早期疾病阶段的治疗方法，阻断疾病进展，并降低个人继续发展为更严重和持久形式的疾病的比例。这项研究是第一次将创新的神经成像方法、神经认知测量方法整合在一起，并在青少年AN合并ASD患者首次出现治疗时建立他们的大脑概况。这将有助于研究临床特征、思维和社会功能风格之间的相互作用。在基线评估中，患有AN的青少年患者、那些已经从障碍中康复的人和年龄匹配的健康人将被要求完成临床和神经心理评估、核磁共振扫描和问卷调查。然后，患有当前AN和康复AN的参与者将被要求在六个月后(治疗后)重复这些措施，以确定可能有助于预测治疗反应或复发的任何差异。我们将使用这些数据来建立一个影响AN的关键因素的数据库，包括认知、情感、脑成像标记物。这项研究以及基于这项研究的未来更大规模的调查将有助于在早期阶段识别最脆弱的患者，以及那些不太可能对当前干预措施做出反应的人。然后，这些发现可能被应用于创建更个性化的支持和治疗策略。

Anorexia Nervosa (AN) is a complex eating disorder, associated with a high physical and psychological risks, it has the highest death rate amongst psychiatric disorders. Treatment resistance is a huge challenge for clinicians and researchers, as approximately 50% of individuals diagnosed with AN do not respond to treatment and go on to develop a more severe and chronic form of the disorder. Research exploring thinking styles and the emotional profile of individuals with AN have demonstrated differences in thinking processes between those with AN and those who have never had an eating disorder. These include tendencies towards an inflexible thinking style, becoming stuck in details and difficulty with social functions such as recognising and expressing emotions and interacting with others. Brain imaging studies have also highlighted different patterns of brain function during these processes in individuals with AN. These difficulties are suggested to be a major contributing factor to the development and maintenance of the disorder. These characteristics are also defining symptoms of Autism Spectrum Disorder (ASD), which has led to research focussing on the overlap between AN and ASD. Although ASD and AN are associated with opposite gender ratios (ASD being more common in males, AN more common in females), recent findings demonstrate that a proportion of adult females with severe and chronic AN have elevated levels of autistic symptoms. Such elevated ASD traits are also associated with poorer treatment outcomes.There is little work focussing on this illness profile at the early stages of the disorder, and research is urgently need to examine both the cognitive and neurobiological profile of young people with AN when they first present with the disorder, also considering the potential role of ASD symptoms in their recovery. Research examining brain activity during thinking and emotional processing has largely been conducted within an adult AN population, and further research is required to explore if there are similar abnormalities and differences in the brain activation of young people with AN, and how this may change as the illness progresses or when weight is restored. Exploring the impact on the brain at first presentation, during the illness and after recovery in young people will help define risk and maintaining factors and help predict treatment outcome. Overall, this work is likely to help develop treatment targeted at early illness stages, disrupt illness progression and reduce the percentage of individual going on to develop a more severe and enduring form of the disorder. This study is the first of its kind to integrate innovative neuroimaging methods, neuro-cognitive measures and to develop profiles of the brain of adolescent AN patients with combined ASD symptoms when they are first presenting for treatment. This will allow for the study of the interaction between clinical features, thinking and social functioning styles. At baseline assessment adolescent patients with AN, those that have recovered from the disorder and age-matched healthy individuals will be asked to complete clinical and neuropsychological assessments, an MRI scan and questionnaires. Participants with current AN and recovered AN will then be asked to repeat these measures six months later (following treatment) to identify any differences in that may help predict treatment response or relapse. We will use this data to build a database of critical factors influencing AN, including cognitive, emotional, brain imaging markers. This research and future larger scale investigations based on this study will help identify the most vulnerable patients at an earlier stage and those individuals unlikely to respond to current interventions. These findings may then be applied to create a more individualised support and treatment strategies.