MICA: Immuno-psychiatry: a consortium to test the opportunity for immunotherapeutics in psychiatry

抑郁症是一种非常常见且潜在严重的疾病。已经有一些治疗抑郁症的方法，比如抗抑郁药SSRI(“百忧解”)。然而，并不是所有的患者对SSRI治疗都有很好的反应：大约三分之一的患者仍然抑郁。这是一个医学领域，迫切需要在治疗方面做得更好。但在过去的15年里，在提供新药方面进展相对缓慢。我们建议探索和测试一种彻底创新的方法来寻找抑郁症(以及潜在的其他精神障碍)的新药物治疗方法。在这个项目中，我们将专注于使用抗炎药物(如阿司匹林)治疗抑郁症的想法，特别是对SSRI治疗反应不佳的患者。最近的科学研究强调，炎症是抑郁症的主要风险因素。某种程度的抑郁在患有类风湿性关节炎等内科炎症性疾病的患者中非常常见。那些主要患有抑郁症且没有内科炎症障碍的患者，其血液中炎症标记物的水平一般比非抑郁症患者要高一些。已经有一些证据表明，炎症可以阻断SSRI抗抑郁药物的治疗效果。已经有一些报告表明，抗炎药物可以起到抗抑郁作用，至少在一些抑郁症患者中是这样。在此基础上，我们将解决4个关键问题，这些问题需要更清楚和完整地回答，然后我们才能考虑潜在的更严重的投资，用于治疗与免疫系统异常状态有关的抑郁症状。1)炎症与SSRI治疗抵抗有关吗？2)抗炎药物有抗抑郁作用吗？这些问题将主要通过对几个大型先前数据集的分析来解决。例如，我们将使用匿名的NHS数据以及工业合作伙伴(葛兰素史克和强生)发布的临床试验数据来寻找新的证据，将炎症与对SSRI治疗反应不佳的抑郁症状联系起来。为了测试炎症可能导致SSRI治疗失败的特定机制原因，我们还将进行一些小型实验室实验，使用来自健康志愿者(爱丁堡大学和葛兰素史克)的血液样本。3)我们能否验证免疫生物标记物对抑郁症和治疗耐药性的影响？4)我们能否使用抑郁症的生物标记物来预测哪些抗炎药物最有可能具有抗抑郁作用？本质上，我们所说的这些问题的意思是，我们能否开发一种血液测试，用来预测哪些有抑郁症状的患者最有可能从哪种抗炎药物中受益？为了解决这些问题，我们将再次优先分析或重新分析现有数据，包括几个大型生物标记物集合(由GSK发布)和由学术合作伙伴(伦敦大学学院、伦敦国王学院)进行的主要研究。我们还将对人体血液样本进行一些额外的实验室实验。我们的目标是在两年内完成这项计划，然后审查是否有理由进一步投资于新的抗炎药物的直接临床试验，用于治疗那些血液测试结果显示他们发炎，对现有抗抑郁药物不太可能产生良好反应的患者。

Depression is a very common and potentially severe disorder. There are some treatments already available for depression, like the SSRI ("Prozac") class of anti-depressants. However, not all patients respond well to SSRI treatment: about a third of patients remain depressed. This is an area of medicine where there is a strong need to do a better job therapeutically. But there has been relatively slow progress in delivering new medicines in the last 15 years. We propose to explore and test a radically innovative approach to finding new drug treatments for depression (and potentially other psychiatric disorders). In this project, we will focus on the idea of using anti-inflammatory drugs (like aspirin) to treat depression, especially in patients who have not responded well to SSRI treatment. Recent scientific research has highlighted that inflammation is a major risk factor for depression. Some degree of depression is very common among patients with medical inflammatory disorders, like rheumatoid arthritis. Patients who are primarily depressed, and do not have a medical inflammatory disorder, generally have somewhat higher blood levels of inflammatory markers than non-depressed people. There is already some evidence that inflammation can block the therapeutic effects of SSRI anti-depressant drugs. And there have been some reports that anti-inflammatory drugs can have anti-depressant effects, at least in some patients with depression.On this basis, we will address 4 key questions that need to be answered more clearly and completely before we can consider potentially more serious investment in clinical development of new anti-inflammatory drugs for depressive symptoms linked to abnormal states of the immune system.1) Is inflammation linked to SSRI treatment resistance? 2) Do anti-inflammatory drugs have anti-depressant effects? These questions will be addressed mainly by analysis of several, large, prior datasets. For example, we will use anonymised NHS data as well as clinical trial data released by the industrial partners (GlaxoSmithKline and Johnson & Johnson) to look for new evidence linking inflammation to depressive symptoms that respond poorly to SSRI treatment. To test a particular mechanistic reason why inflammation might cause SSRI treatment failure, we will also do a number of small lab experiments, using blood samples from healthy volunteers (University of Edinburgh and GSK).3) Can we validate immune biomarkers for depression and treatment resistance? 4) Can we use biomarkers of depression to predict which anti-inflammatory drugs are most likely to be anti-depressant? Essentially what we mean by these questions is can we develop a blood test that we can use to predict which patients with depressive symptoms are most likely to benefit from which anti-inflammatory drug? To address these questions we will again priortise analysis or re-analysis of existing data including several large biomarker collections (released by GSK) and major studies conducted by the academic partners (University College London, King's College London). We will also conduct some additional lab experiments on human blood samples.We aim to complete this project within 2 years and then review the case for further investment in direct clinical trials of new anti-inflammatory drugs for treatment of depression in patients who have a blood test result indicating that they are inflamed and unlikely to respond well to existing anti-depressant drugs.