Clinical Psychopharmacology of 5-HT

临床抑郁症是一种常见病，通常开始于成年早期，可能在一生中反复发作。临床抑郁症的复发性及其给患者及其家属带来的负担，使其成为痛苦和残疾的主要医学原因之一。了解抑郁症患者大脑的生化变化将有助于我们设计出更好的治疗方法，并加强预防工作。一种叫做5-羟色胺（5-HT）的神经递质在抑郁症的病因和目前的药物治疗中都起着重要作用。在这项研究中，我们将利用先进的脑成像技术来研究5-羟色胺是如何在大脑中改变情绪的。例如，我们将使用磁共振波谱（MRS）来观察5-羟色胺如何与大脑中使用谷氨酸盐化学信使的特殊神经元相互作用。我们相信5羟色胺和谷氨酸之间的相互作用可能对帮助我们了解抑郁症的原因和开发更有效的治疗方法非常重要。抑郁症治疗的一个主要问题是对当前药物治疗的反应的不可预测性；一些病人做得很好，另一些没有得到很大的帮助。我们认为，通过5-羟色胺起作用的抗抑郁药，如选择性5-羟色胺再摄取抑制剂（SSRIs），可能通过作用于大脑分析情绪信息的方式来产生治疗效果。功能性磁共振成像（fMRI）的使用使我们能够检查与情绪体验有关的大脑网络。因此，我们将使用功能磁共振成像来研究抑郁症患者的这些大脑网络如何受到SSRIs的影响，以及我们所看到的变化是否使我们能够预测那些治疗效果良好的患者。

Clinical depression is a common illness, often beginning in early adulthood, which can recur throughout a lifetime. The recurrent nature of clinical depression, together with the burden it places on patients and their families, makes this condition one of leading medical causes of suffering and disability. Understanding the biochemical changes in the brain in depression will help us devise better treatments and also improve efforts at prevention. A neurotransmitter called serotonin (5-HT) plays an important role in both the causation of depression and in current drug treatments. In this study we will use advances in brain imaging to study how 5-HT acts in the brain to alter mood. For example we will use magnetic resonance spectroscopy (MRS) to see how 5-HT interacts with special neurons in the brain that use a chemical messenger called glutamate. We believe that the interactions between 5 HT and glutamate may be very important in helping us understand the cause of depression and in developing more effective methods of treatment. A major problem in the treatment of depression is the unpredictability of response to current drug treatments; some patients do well, others are not helped very much. We believe that antidepressants which work through 5-HT such as the selective serotonin re-uptake inhibitors (SSRIs) may produce their therapeutic effects by acting on the way the brain analyses emotional information. The use of functional magnetic resonance imaging (fMRI) allows us to examine the brain networks involved in emotional experience. We will use therefore use fMRI to study how these brain networks are influenced by SSRIs in depressed patients and whether the changes we see enable us to predict those patients who will do well with treatment.