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，在生命中的某个时刻，多达四分之一的人会受到影响。尽管抑郁症对个人和社会造成了毁灭性的影响，但我们对一个人在临床上患抑郁症时大脑发生了什么，或者抗抑郁药物是如何起作用的知之甚少。我们知道，血清素是大脑中的一种化学信使，对控制我们的情绪(无论我们是高兴还是悲伤)都很重要，而且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，可能需要几周的时间才能感觉好一些，或者为什么有些人对治疗的反应很好，而另一些人的反应很差或根本没有。目前这项研究提案的主要目的是更好地了解抗抑郁药物在大脑中的作用，以及我们如何使其更有效。我们已经证明，大脑中一个非常小、基本上被忽视的部分，称为缰核，在控制大脑中的5-羟色胺水平方面非常重要，特别是当人们第一次开始服用抗抑郁药物时。我们的部分研究将使用功能磁共振成像(一种允许我们看到？)的技术来研究这种控制途径。研究以特定方式作用于5-羟色胺系统的药物是否也改变了这一途径的运作方式。如果我们可以的话？关掉？通过这种控制途径，我们或许能够制造出见效更快的抗抑郁药物。缰核还与动力和奖励有关，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失)。这些非享乐症患者有时也是最难治疗的。多巴胺是大脑的另一种化学信使，S化学信使，它对奖赏处理非常重要，我们认为缰核可能通过与5-羟色胺的相互作用来控制多巴胺的释放。我们研究的另一部分将用功能磁共振成像来观察这些多巴胺/5-羟色胺的相互作用。如果我们能够了解缰核是如何与多巴胺相互作用的，我们可能就能更好地帮助那些快感缺乏症水平非常高的抑郁症患者。

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.