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

青春期和青壮年是对各种有害和危险行为高度脆弱的时期，因为负责抑制冲动和危险行为的大脑回路还没有完全成熟。冲动控制问题以及发展为以有害的过度消费(如药物或食物)为特征的更严重的强迫行为障碍是一个特别令人关切的问题，因为它们是世界上可预防的发病率和死亡率最高的。暴饮暴食障碍(Bed)就是这些障碍的一个例子，即抵抗食物的能力--或者一旦暴饮暴食开始就停止进食--的能力受到了损害。卧床是最常见的饮食失调，通常始于青春期。然而，它是一个慢性问题，在发病后持续多年，并导致各种严重的精神和新陈代谢健康问题。虽然BED受到神经科学研究人员的关注相对较少，但Bed和物质使用障碍(SUDS)之间有惊人的相似之处，后者通常也会在青春期发展，一直是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赏记忆--“不适应奖赏记忆”(MRM)--构成了对毒品的渴望，以及在遇到“触发线索”时寻找和使用毒品的倾向。再加上在抑制这些线索引发的反应方面的缺陷，MRM导致持续的药物使用复发。鉴于肥皂水和床之间在行为、症状、发病年龄和共病方面的重叠，磁共振成像可能也在暴饮暴食对食物提示的反应中发挥关键作用。对床的心理治疗通常依赖于在食物暗示和新的、更有帮助的行为之间形成替代联系。这些药物与食品相关的MRM相互竞争并暂时受到抑制。然而，这种治疗不会直接削弱MRM，因此MRM通常会随着时间的推移重新占据主导地位，导致复发。相比之下，最近的发现表明，使用行为技术直接针对MRM是可能的，这种技术很容易被改造成用于卧床者的治疗。特别是，有可能重新激活MRM，这是一个短暂地让这些记忆变得柔韧的过程，然后教会新的联想，将MRM‘重写’成一种适应性形式，不会促进暴饮暴食行为，防止复发。这种方法现在已经在酗酒者、吸烟者和海洛因使用者中进行了测试，并被证明是一种非常有希望的策略，可以减少吸毒者对毒品线索的反应。在这个项目中，我们将把这一令人兴奋的新方法应用到暴饮者身上，并确定是否在对食物提示的反应和对暴饮暴食行为的反应中也发现了类似的影响。我们将测试两种重写与食物相关的MRM的方法，每一种方法都针对被认为在床上很重要的不同神经机制，即1)减少暴饮暴食线索引发渴望和暴饮暴食的能力，以及2)增加由这些线索引发的停止食物消耗的能力。通过测试“高危”人群的年轻人，我们将瞄准一个发育期，症状开始出现，早期干预可能会产生特别强大的效果，因为与食品相关的MRM网络仍然相对“年轻”。重要的是，在测试这些新的、潜在强大的技术的早期阶段，将研究参与者的风险降至最低是至关重要的。因此，我们的研究对象将是那些表现出暴饮暴食行为但没有严重饮食或其他心理障碍的年轻人。如果我们证明了与食品相关的MRM重写的证据，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，用于寻求床上帮助的人，以及可能与此相关的问题，如肥胖或暴食症。

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.