Nerurkar Louis, Siebert Stefan, McInnes Iain B, Cavanagh Jonathan
Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, UK.
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Lancet Psychiatry. 2019 Feb;6(2):164-173. doi: 10.1016/S2215-0366(18)30255-4. Epub 2018 Oct 23.
The coexistence of immune-mediated inflammatory diseases with depression has long been recognised. Data that illustrate the intimate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores. In this Review, we assess this evidence in relation to rheumatoid arthritis and depression, with a focus on innate immune and molecular responses to inflammation, and discuss the challenges of assessing causation in this population, acknowledging the difficulty of assessing the confounding and contributory effects of pain and fatigue. We also discuss how future clinical and preclinical research might improve diagnosis of depression in people with rheumatoid arthritis and shed light on mechanisms that could be substrates for therapeutic interventions.
免疫介导的炎症性疾病与抑郁症的共存早已得到认可。阐明外周免疫反应与大脑免疫反应之间密切关联的数据，增加了共享病理生理机制的可能性。这些关联包括促炎细胞因子对单胺能神经传递、神经营养因子以及突触可塑性指标的负面影响。支持这种关联的证据正在不断积累，包括免疫调节治疗临床试验的结果，表明这些干预措施能够在不改善身体疾病评分的情况下对心理健康有益。在本综述中，我们评估了与类风湿关节炎和抑郁症相关的这一证据，重点关注对炎症的固有免疫和分子反应，并讨论了在该人群中评估因果关系的挑战，同时认识到评估疼痛和疲劳的混杂及促成作用存在困难。我们还讨论了未来的临床和临床前研究如何可能改善类风湿关节炎患者抑郁症的诊断，并阐明可能作为治疗干预靶点的机制。
