MICA: The Translational, Computational and Neurocognitive Basis of Anxiety

每四个人中就有一个人在某一年会遭受某种形式的心理健康问题的困扰。对于我们大多数人来说，这将是某种形式的焦虑或压力相关的问题。有些人的焦虑是如此严重，以至于他们最终只能呆在家里。焦虑每年给英国经济造成超过140亿英镑的损失。我们目前有有效的临床治疗方法，包括心理治疗(即治疗)和药物治疗(即药物治疗)，可以治疗焦虑。然而，我们目前还不能有效地针对有反应的人进行这些治疗。事实上，对于大多数人来说，他们尝试的第一种治疗方法不会奏效。更令人担忧的是，对于高达25%的患者来说，我们目前的治疗方法都不起作用。我们有这些针对治疗的问题至少有两个原因：i)我们不知道我们目前的治疗在生物水平上是如何起作用的；ii)我们不知道潜在的生物因素是如何产生令人衰弱的焦虑感的。如果不能更好地了解这两个问题，我们就不会提高针对治疗的能力。因此，这一奖学金旨在提高我们对焦虑症状和治疗的生物学基础的理解。它侧重于心理治疗，旨在更好地了解1)心理治疗的神经回路；2)开发新的心理治疗方法；3)更好地理解焦虑诊断的生物学基础。具体地说：1)神经回路：在过去的十年里，我发现了一种驱动焦虑感觉的大脑回路，但我们不知道它在治疗后是否会改变。在这个项目中，我将扫描正在接受焦虑心理治疗的焦虑患者的大脑，并将他们与没有接受治疗的焦虑患者进行比较。如果我们证明同样的回路对治疗反应很重要，它将使我们能够更好地针对个人进行治疗，并减少尝试不起作用的治疗方法的人数。2)治疗：同时，我将尝试开发一种新的治疗焦虑的计算机化方法。这是可能的，因为我在一个被称为计算精神病学的新领域的进步给了我们更好的工具，让我们更好地洞察大脑的计算过程，以及它们在焦虑症中是如何变化的。因此，我将开发一种针对这些计算过程的计算机化培训程序，并在治疗研究中进行测试。如果这种方法奏效，它将提供一种可以通过智能手机提供的快速且经济有效的治疗方法，并最终减少患焦虑症的人数。3)诊断：最后，我将努力提高我们对令人衰弱的焦虑感最初是如何出现的理解。越来越清楚的是，我们目前的诊断是基于症状清单的，并没有真正反映出单独的生物学类别。因此，我将寻找会引发焦虑但跨越我们当前类别的“跨诊断”维度。我将通过让数千人在线完成一项简单的心理任务来做到这一点，我之前曾将这项任务与令人衰弱的焦虑联系在一起。此外，我们还将从这些人那里收集广泛的其他心理任务和问卷。将最先进的统计方法应用于这些“大数据”，将使我们能够识别导致焦虑症状的跨诊断维度。从长远来看，这些新的跨诊断维度将提高我们确定驱动症状的生物因素的能力，从而帮助我们预测治疗反应并开发新的治疗方法。总而言之，我将结合我独特的跨学科技能，以及我在描绘焦虑的神经和计算基础方面的突破，开发新的、更有效的临床工具来诊断和治疗焦虑，最终目标是提高数百万患者的生活质量。

One in four of us will suffer from some form of mental health problem in a given year. For the majority of us, this will be some form of anxiety or stress related problem. Some people's anxiety is so crippling that they end up housebound. Anxiety costs the UK economy over £14 billion a year.We currently have effective clinical treatments, both psychological (i.e. therapy) and pharmacological (i.e. medication), that can treat anxiety. However, we are not currently able to effectively target these treatments to people who will respond. In fact, for most people, the first treatment that they try will not work. Even more worrying is that for up to 25% of sufferers; none of our current treatments will work.There are at least two reasons that we have these problems targeting treatments:I) We do not know how our current treatments work at a biological levelII) We do not know how debilitating feelings of anxiety emerge from the underlying biology.Without a better understanding of both of these issues we will not improve our ability to target treatments. This fellowship therefore seeks to improve our understanding of the biological basis of anxiety symptoms and treatments. It focuses on psychological treatments and aims to better understand 1) the neural circuitry by which psychological treatment works; 2) develop new psychological treatments; and 3) better refine our understanding of the biological bases of anxiety diagnosis. Specifically:1) Neural Circuitry:Over the last decade, I have identified a brain circuit which drives feelings of anxiety but we do not know if it changes following treatment. In this project I will scan the brains of anxious people undergoing psychological treatment for anxiety and compare them to anxious people who are not. If we show that this same circuit is important for treatment response, it will enable us to better target treatments to individuals, and reduce the number of people who try treatments that do not work for them.2) Treatments:In parallel with this I will attempt to develop a new computerised treatment for anxiety. This is possible because my advances in a new field known as computational psychiatry have given us tools that provide better insight into the computational process of the brain, and how they change in anxiety disorders. I will therefore develop a computerised training procedure that targets these computational processes and test it in a treatment study. If this works, it will provide a quick and cost effective treatment that could be delivered by smartphones and ultimately reduce the number of individuals suffering from anxiety.3) Diagnosis:Finally, I will try to improve our understanding of how debilitating feelings of anxiety emerge in the first place. It is increasingly clear that our current diagnoses, which are based on symptom checklists, do not reflect truly separate biological categories. I will therefore search for 'trans-diagnostic' dimensions that drive anxiety but which cut across our current categories. I shall do this by getting thousands of people to complete a simple psychological task online that I have previously linked to debilitating anxiety. In addition, we will collect a wide range of other psychological tasks and questionnaires from these people. Applying state-of-the-art statistical methods to this 'big data' will enable us to identify trans-diagnostic dimensions that drive anxiety symptoms. In the long term these new trans-diagnostic dimensions will improve our ability to determine the biological factors driving symptoms and hence help us predict treatment response and develop new treatments.In sum, I will combine my unique inter-disciplinary skill-set, with my breakthroughs in delineating the neural and computational basis of anxiety, to develop new and more effective clinical tools for anxiety diagnosis and treatment, with the ultimate goal of improving the quality of life for millions of sufferers.