Clinical Psychopharmacology of 5-HT

临床抑郁症是一种常见疾病，通常始于成年早期，可在一生中反复发作。临床抑郁症的反复发作，加上它给患者及其家人带来的负担，使这种疾病成为导致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更好的治疗方法，并提高预防力度。一种名为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扮演着重要的角色。在这项研究中，我们将利用大脑成像的进展来研究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一种名为谷氨酸的化学信使的特殊神经元相互作用。我们认为，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。抑郁症治疗中的一个主要问题是对当前药物治疗的反应不可预测；一些患者表现良好，另一些患者则没有得到太大帮助。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产生治疗效果。功能磁共振成像(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SSRI的影响，以及我们所看到的变化是否使我们能够预测哪些患者将获得良好的治疗。

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.