Clinical Psychopharmacology of Depression

临床抑郁症很常见，有时很难成功治疗。我们需要为抑郁症患者开发更好的药物治疗方法，但由于缺乏对疾病所涉及的脑化学的了解，这一目标受到阻碍。两个重要的化学信使，血清素和谷氨酸，被认为是参与抑郁症，在本研究中，我们将使用两种先进的成像技术，正电子发射断层扫描（PET）和磁共振波谱（MRS），以增加我们的知识，这些化学物质是如何参与抑郁症及其治疗。我们还将把我们的发现与炎症的测量联系起来，因为一些抑郁症患者的血液中似乎有炎症变化，炎症会影响血清素和谷氨酸。如果我们能够测量5-羟色胺在活体人脑中的释放，这将极大地增加我们对5-羟色胺在抑郁症中的作用的理解。在一个项目中，我们将尝试通过对健康志愿者的5-羟色胺受体的特定标记进行PET成像来实现这一目标，这些志愿者的大脑5-羟色胺水平因饮食控制而暂时降低。我们将使用MRS来研究大脑谷氨酸水平。我们将首先研究正在接受抗病毒药物干扰素治疗病毒性疾病的肝炎患者。干扰素在治疗肝炎时会引起抑郁，我们将对抑郁进行评级，并观察干扰素治疗期间脑谷氨酸的变化。然后，我们将使用相同的MRS检查来观察临床抑郁症患者的谷氨酸水平。我们将使用一种称为CRP的血液测试将患者分为有明显炎症和没有炎症的患者。然后我们将观察炎症患者的谷氨酸变化是否与干扰素治疗患者相似。抑郁症患者对SSRIs常规抗抑郁治疗的反应差异很大。因此，我们将观察炎症的存在是否会影响对SSRI药物艾司西酞普兰的反应。我们预测，治疗前CRP水平高的患者抗抑郁治疗效果较差。如果是这样的话，CRP可能成为一个有用的临床标志物，以决定谁将与标准的抗抑郁药治疗。

Clinical depression is common and sometimes difficult to treat successfully. We need to develop better pharmacological treatments for depressed patients but this goal is hindered by a lack of knowledge of the brain chemistry involved in the illness. Two important chemical messengers, serotonin and glutamate, are thought to be involved in depression and in the present investigation we will use two advanced imaging techniques, positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) to increase our knowledge of how these chemicals are involved in depression and its treatment. We will also link our findings to measures of inflammation because some depressed patents appear to have inflammatory changes in their blood and inflammation can affect serotonin and glutamate. It will greatly increase our understanding of the role of serotonin in depression if we could measure its release in the living human brain and in one project we will try to achieve this using PET imaging of a specific label of serotonin receptors in healthy volunteers whose brain serotonin levels have been temporarily lowered by a dietary manipulation. We will use MRS to investigate levels of brain glutamate. We will first study patients with hepatitis who are receiving the anti-viral agent, interferon, for the treatment of their viral disorder. Interferon is known to cause depression when it is used to treat hepatitis and we will make ratings of depression and look at changes in brain glutamate during interferon treatment. We will then use the same MRS examination to look at glutamate levels in patients with clinical depression. We will use a blood test called CRP to divide the patients up into those with significant inflammation and those without. We will then see whether the changes in glutamate in patients with inflammation resemble those seen in patients treated with interferon.The response of depressed patients to conventional antidepressant treatment with SSRIs is quite variable. We will therefore see whether the presence of inflammation affects the response to the SSRI drug, escitalopram. We predict that patients with high levels of CRP before treatment will do less well with antidepressant therapy. If this is the case CRP could become a useful clinical marker to decide who will do well with standard antidepressant treatment.