Understanding maladaptive reward memory in young people who binge eat: Application of novel insights from addiction

青春期和青年期是对各种有害和危险行为的高度脆弱性时期，因为负责抑制冲动和危险行为的大脑回路尚未完全成熟。冲动控制问题以及以有害的过度消费（如药物或食物）为特征的更严重的强迫行为障碍的进展是一个特别令人关切的问题，因为它们是全世界可预防的发病率和死亡率最高的原因。暴食症（BED）是这些疾病的一个例子，在这种疾病中，抵抗食物的能力——或者一旦暴饮暴食开始就停止进食的能力——受到损害。BED是最普遍的饮食失调症，通常始于青春期。然而，这是一个慢性问题，在发病后持续多年，并导致各种严重的精神和代谢健康问题。虽然BED受到神经科学研究人员的关注相对较少，但BED与物质使用障碍（sud）之间存在惊人的相似之处，后者通常也发生在青少年时期，并已成为广泛的基础神经科学、临床和理论研究的主题。这表明，在吸毒过程中形成的异常强烈的奖励记忆——“适应性不良奖励记忆”（MRMs），是毒品渴望和在遇到“触发线索”时寻求和使用毒品的倾向的基础。再加上抑制这些线索引发的反应的缺陷，MRMs导致持续的吸毒复发。考虑到sud和BED在行为、症状、发病年龄和合并症方面的重叠，MRMs也可能在对食物线索的反应中暴饮暴食中发挥关键作用。BED的心理治疗通常依赖于食物线索和新的、更有益的行为之间的替代关联的形成。它们与食物相关的mrm竞争并暂时抑制它们。然而，这些治疗并不能直接削弱mrm，因此随着时间的推移，mrm通常会重新占据主导地位，导致复发。相比之下，最近的发现表明，使用行为技术直接靶向MRMs是可能的，这种技术可以很容易地用于治疗BED患者。特别是，有可能“重新激活”MRM，这一过程会短暂地使这些记忆变得柔韧，然后教授新的联想，将MRM“重写”成一种适应性形式，不会促进暴食行为，防止复发。这种方法已经在酗酒者、吸烟者和海洛因使用者身上进行了测试，并被证明是一种非常有前途的策略，可以减少成瘾者对毒品线索的反应。在这个项目中，我们将把这种令人兴奋的新方法应用到暴饮暴食者身上，并确定是否在对食物线索的反应和暴饮暴食行为中发现了类似的效果。我们将测试两种重写食物相关MRMs的方法，每种方法都针对被认为在BED中重要的不同神经机制，即1)减少暴食线索引发渴望和暴食的能力，2)增加停止这些线索引发的食物消耗的能力。通过对“有风险”的年轻人进行测试，我们将针对症状开始出现的发育时期，早期干预可能会产生特别强大的效果，因为与食物相关的MRM网络仍然相对“年轻”。重要的是，在测试这些潜在强大的新技术的早期阶段，将研究参与者的风险降到最低是至关重要的。因此，我们的研究对象将是那些有暴食行为但没有严重饮食或其他心理障碍的年轻人。如果我们证明了食物相关mrm的重写证据，我们的发现将具有重要的治疗意义。下一步将是调整这些实验策略，用于寻求BED帮助的人，以及可能相关的问题，如肥胖或贪食症。

Adolescence and young adulthood are periods of heightened vulnerability to a variety of harmful and risky behaviours, as the brain circuits responsible for inhibiting impulsive and risky behaviours are not fully matured. Impulse control problems, and the progression to more serious compulsive-behavioural disorders characterised by harmful overconsumption (e.g. of drugs or food) are a particular concern since they account for the highest levels of preventable morbidity and mortality throughout the world. Binge eating disorder (BED) is an example of these disorders, in which the ability to resist food - or to stop eating once an episode of overeating has begun - is impaired. BED is the most prevalent eating disorder and typically begins in adolescence. However, it is a chronic problem, lasting for many years after onset and contributing to a variety of serious psychiatric and metabolic health problems. While BED has received relatively little attention from neuroscientific researchers, there are striking parallels between BED and substance use disorders (SUDs), which also typically develop in adolescence and have been the subject of extensive basic neuroscientific, clinical and theoretical research. This has shown that abnormally strong reward memories - 'maladaptive reward memories' (MRMs) - formed during drug-use underlie drug craving and the propensity to seek and use drugs when 'trigger cues' are encountered. Coupled with deficits in inhibiting the responses sparked by these cues, MRMs cause continued relapse to drug use. Given the overlap in the behaviours, symptoms, age of onset and comorbidity between SUDs and BED, MRMs also likely play a key role in binge eating in response to food cues. Psychological treatments for BED often rely on the formation of alternative associations between food cues and new, more helpful behaviours. These compete with and temporarily suppress food-related MRMs. However, such treatments do not directly weaken MRMs, and as a result MRMs typically regain dominance over time, resulting in relapse. In contrast, recent discoveries suggest that it is possible to directly target MRMs using behavioural techniques that could readily be adapted for use in therapy for people with BED. In particular, it is possible to 'reactivate' MRMs, a process which briefly makes these memories pliable, and then to teach new associations that 'rewrite' the MRM into an adaptive form that does not promote bingeing behaviour and prevents relapse. This approach has now been tested in heavy drinkers, smokers and heroin users, and shown to be a very promising strategy for reducing addicts' responses to drug cues. In this project, we will apply this exciting new approach to binge-eaters and determine whether similar effects are found in response to food cues, and on bingeing behaviour. We will test two methods for rewriting food-related MRMs, each targeting a different neural mechanism thought to be important in BED, namely 1) reducing the ability of binge food cues to trigger craving and bingeing and 2) increasing the ability to stop food consumption triggered by these cues. By testing an 'at-risk ' population of young people, we will be targeting a developmental period when symptoms are beginning to emerge and early intervention might be expected to have an especially powerful effect, as food-related MRM networks are still relatively 'young'. Importantly, at this early stage of testing these new and potentially powerful techniques, it is essential to minimise risk to research participants. As such, our studies will be with young people who show binge eating behaviour but do not have a severe eating- or other psychological disorder. If we demonstrate evidence of rewriting of food-related MRMs, our findings will have important treatment implications. The next step will be to adapt these experimental strategies for use in people seeking help for BED, and possibly related problems like obesity or bulimia.