Modelling human habenula-5-HT2C interactions with high field-strength (7T), high-resolution pharmacological FMRI

抑郁症是一种严重的、使人衰弱的疾病，多达四分之一的人在一生中的某个阶段会受到影响。尽管抑郁症对个人和社会造成了毁灭性的影响，但当一个人临床上患上抑郁症时，大脑会发生什么，以及抗抑郁药物是如何起作用的，我们知之甚少。我们知道血清素，大脑中的一种？血清素是一种化学信使，对控制我们的情绪（我们是高兴还是悲伤）很重要，大多数用于治疗抑郁症的药物都作用于血清素。我们不知道的是，为什么一个人一旦开始服用抗抑郁药，要过好几个星期才能感觉好些，或者为什么有些人对治疗反应很好，而有些人反应很差，甚至根本没有反应。目前研究计划的主要目的是更好地了解抗抑郁药在大脑中的作用，以及我们如何使它们更有效。我们已经证明，大脑中有一个很小的、基本上被忽视的部分叫做缰状核，它在控制大脑中血清素的水平方面非常重要，尤其是当人们第一次开始服用抗抑郁药的时候。我们的部分研究将使用功能性磁共振成像（一种允许我们“看到”的技术）来研究这种控制途径。（大脑活跃的地方）来研究以特定方式作用于血清素系统的药物是否也会改变这一途径的功能。如果可以的话？关掉吗?通过这种控制途径，我们或许可以制造出更快起作用的抗抑郁药物。缰带也与动机和奖励有关，一些抑郁症患者缺乏动力，经常对奖励事件表现出减少或迟钝的反应（精神病学家称之为快感缺乏）。这些快感缺乏症患者有时也是最难治疗的。多巴胺，大脑的另一个部分？这是一种化学信使，对奖励处理非常重要，我们认为缰状核可能通过与血清素的相互作用来控制多巴胺的释放。我们研究的另一部分将通过功能性磁共振成像研究多巴胺/血清素的相互作用。如果我们能理解缰状核是如何与多巴胺相互作用的，我们就能更好地帮助那些重度快感缺乏症的抑郁症患者。

Depression is a serious and debilitating disease that can affect as many as 1 in 4 people at some point in their life. Despite the devastating impact of depression on individuals and society, we know very little about what happens in the brain when a person becomes clinically depressed, or how antidepressant medications work. We do know that serotonin, one of the brain?s chemical messengers, is important in controlling our mood (how happy or sad we are) and most of the drugs used to treat depression act on serotonin. What we do not know is why it can take many weeks for a person to feel better once they start taking an antidepressant, or why some people respond very well to treatment while others respond poorly or not at all. The principal aim of the current research proposal is to better understand what antidepressants do in the brain and how we can make them more effective. We have shown that a very small and largely ignored part of the brain called the habenula is very important in controlling the levels of serotonin in the brain, especially when people first start to take antidepressants. Part of our research will look at this control pathway using Functional Magnetic Resonance Imaging (a technique that allows us to ?see? where the brain is active) to investigate if drugs that act in a particular way on the serotonin system also change the way this pathway functions. If we can ?switch off? this control pathway we may be able to make antidepressant drugs that work more quickly. The habenula is also involved in motivation and reward, and some depressed patients lack drive and often show reduced or blunted responses to rewarding events (psychiatrists call this anhedonia). These anhedonic patients are also sometimes the most difficult to treat. Dopamine, another of the brain?s chemical messengers, is very important for reward processing and we think that the habenula may control the release of dopamine through interactions with serotonin. Another part of our research will look at these dopamine/serotonin interactions with Functional Magnetic Resonance Imaging. If we can understand how the habenula interacts with dopamine, we may be able to better help those depressed patients who have very high levels of anhedonia.