Cavanagh Jonathan T
Centre for Immunobiology, School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Curr Top Behav Neurosci. 2024;66:217-231. doi: 10.1007/7854_2023_459.
The last two decades have seen a flourishing of research into the immunobiology of psychiatric phenotypes, in particular major depressive disorder. Both preclinical and clinical data have highlighted pathways and possible mechanisms that might link changes in immunobiology, most especially inflammation, to clinically relevant behaviour. From a therapeutics perspective, a major impetus has been the action of Biologics, often monoclonal antibodies, that target specific cytokines acting as "molecular scalpels" helping to uncover the actions of those proteins. These interventions have been associated with improvements in mood and related symptoms. There are now enough studies and participants to permit meta-analytic analyses of the actions of these and other anti-inflammatory agents.In this chapter, the focus is on the evidence for the role of inflammation biology in depression and the meta-analytic data from trials. The putative mechanisms that might underpin the antidepressant effect of anti-inflammatory drugs are also explored. Lastly, I describe the more stubborn difficulties around heterogeneity, deep phenotyping and stratification as well as improved animal models and greater understanding of the biology that might be addressed by future studies.
在过去二十年中，对精神疾病表型，尤其是重度抑郁症的免疫生物学研究蓬勃发展。临床前和临床数据均突出了可能将免疫生物学变化（尤其是炎症）与临床相关行为联系起来的途径和潜在机制。从治疗学角度来看，一个主要的推动力是生物制剂（通常是单克隆抗体）的作用，这些生物制剂靶向特定细胞因子，充当“分子手术刀”，有助于揭示这些蛋白质的作用。这些干预措施与情绪及相关症状的改善有关。现在有足够的研究和参与者来对这些及其他抗炎药物的作用进行荟萃分析。在本章中，重点是炎症生物学在抑郁症中的作用证据以及试验的荟萃分析数据。还探讨了可能是抗炎药物抗抑郁作用基础的潜在机制。最后，我描述了围绕异质性、深度表型分析和分层以及改进动物模型和对生物学的更深入理解等更棘手的难题，未来研究可能会解决这些问题。
