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

MICA：免疫精神病学：一个测试精神病学免疫治疗机会的联盟

• 批准号: MR/L014815/1
• 负责人: Edward Bullmore
• 金额: $ 63.38万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL014815%2F1
• 关键词: MICA; Immuno; psychiatry; consortium; test

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.

抑郁症是一种非常常见和潜在的严重疾病。有一些治疗抑郁症的方法，如SSRI（百忧解）类抗抑郁药。然而，并非所有患者对SSRI治疗反应良好：约三分之一的患者仍然抑郁。这是一个强烈需要在治疗上做得更好的医学领域。但过去15年来，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疾病）的新药物治疗。在这个项目中，我们将重点关注使用抗炎药（如阿司匹林）治疗抑郁症的想法，特别是在对SSRI治疗反应不佳的患者中。最近的科学研究强调，炎症是抑郁症的主要危险因素。某种程度的抑郁症在患有医学炎症性疾病的患者中非常常见，如类风湿性关节炎。原发性抑郁症患者，没有医学炎症性疾病，通常比非抑郁症患者血液中的炎症标志物水平略高。已经有一些证据表明，炎症可以阻断SSRI抗肿瘤药物的治疗作用。而且之前也有一些报道称，消炎药可以起到抗抑郁的作用，至少在部分抑郁症患者身上是这样的，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，然后我们才能考虑对与免疫系统异常状态相关的抑郁症状的新抗炎药物的临床开发进行潜在的更认真的投资。炎症与SSRI治疗抵抗有关吗？2)消炎药有抗抑郁作用吗？这些问题将主要通过分析几个大型的先前数据集来解决。例如，我们将使用匿名的NHS数据以及工业合作伙伴（葛兰素史克和约翰逊&约翰逊）发布的临床试验数据，以寻找将炎症与对SSRI治疗反应不佳的抑郁症状联系起来的新证据。为了测试炎症可能导致SSRI治疗失败的特定机制原因，我们还将使用健康志愿者（爱丁堡大学和GSK）的血液样本进行一些小型实验室实验。4)我们能否利用抑郁症的生物标志物来预测哪些抗炎药最有可能抗抑郁？这些问题本质上是指我们能否开发一种血液检测方法来预测哪些抑郁症患者最有可能从哪种抗炎药中获益？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志物集合（由GSK发布）和学术合作伙伴（伦敦大学学院，伦敦国王学院）进行的主要研究。我们还将对人类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该项目，然后审查进一步投资新抗炎药物的直接临床试验的案例，这些药物用于治疗血液检查结果显示患有炎症且对现有抗炎药物不太可能有良好反应的患者的抑郁症。

项目成果

Genetic Contributions of Inflammation to Depression.

• DOI: 10.1038/npp.2016.169
• 发表时间: 2017-01
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Identifying the women at risk of antenatal anxiety and depression: A systematic review.

• DOI: 10.1016/j.jad.2015.11.014
• 发表时间: 2016-02
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Biaggi A;Conroy S;Pawlby S;Pariante CM
• 通讯作者: Pariante CM

Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults.

• DOI: 10.1038/tp.2017.155
• 发表时间: 2017-08-15
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Bell JA;Kivimäki M;Bullmore ET;Steptoe A;MRC ImmunoPsychiatry Consortium;Carvalho LA
• 通讯作者: Carvalho LA

The role of soluble epoxide hydrolase and its inhibitors in depression.

• DOI: 10.1016/j.bbih.2021.100325
• 发表时间: 2021-10
• 期刊: Brain, behavior, & immunity - health
• 作者: Borsini A

Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?

• DOI: 10.1007/s00213-015-4105-9
• 发表时间: 2016-05
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Boorman E;Zajkowska Z;Ahmed R;Pariante CM;Zunszain PA
• 通讯作者: Zunszain PA