Sørensen Nina Vindegaard, Benros Michael Eriksen
Biological and Precision Psychiatry, Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Hellerup, Denmark.
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Curr Top Behav Neurosci. 2023;61:15-34. doi: 10.1007/7854_2022_369.
Depression is a frequent mental disorder with a substantial contribution to years lived with disability worldwide. In the search for new treatment targets, the immune system's contribution to the pathogenesis of depression has received increased attention as immune activation has been associated with depression in various epidemiological and case-control studies. Epidemiological studies have shown that immune exposures such as severe infections and autoimmune disorders increase the risk of depression. Furthermore, immune system activation has been indicated in case-control studies of depression revealing higher levels of key pro-inflammatory cytokines among patients with depression than healthy controls, particularly in blood and to some extent in the cerebrospinal fluid. Moreover, brain imaging studies indicate increased microglial activity during depression, and gut microbiota studies have documented alterations of gut microbiota composition to be associated with depression. Based on findings from animal and human studies, several immune-mediated molecular mechanisms have been suggested to underlie the association between increased immunological activity and depression. However, the research is challenged by the heterogeneity of the depression diagnosis and - to some extent - the precision of currently available technology for immune biomarker quantification, particularly regarding the assessment of low-grade neuroinflammation. Nonetheless, an enhanced understanding of the complex interactions between the immune system and the brain in the context of depression could pave the way for precision medicine approaches with immune-modulating treatment as a promising additional option in the treatment of depression.
抑郁症是一种常见的精神障碍，在全球范围内对失能生存年数有重大影响。在寻找新的治疗靶点过程中，免疫系统对抑郁症发病机制的作用受到了更多关注，因为在各种流行病学和病例对照研究中，免疫激活都与抑郁症有关。流行病学研究表明，诸如严重感染和自身免疫性疾病等免疫暴露会增加患抑郁症的风险。此外，抑郁症的病例对照研究表明存在免疫系统激活，抑郁症患者体内关键促炎细胞因子的水平高于健康对照组，特别是在血液中，在一定程度上在脑脊液中也是如此。而且，脑成像研究表明抑郁症期间小胶质细胞活性增加，肠道微生物群研究已证明肠道微生物群组成的改变与抑郁症有关。基于动物和人体研究的结果，有人提出几种免疫介导的分子机制是免疫活性增加与抑郁症之间关联的基础。然而，该研究面临抑郁症诊断异质性以及——在一定程度上——当前可用的免疫生物标志物定量技术精度的挑战，特别是在评估低度神经炎症方面。尽管如此，在抑郁症背景下增强对免疫系统与大脑之间复杂相互作用的理解，可能为精准医学方法铺平道路，将免疫调节治疗作为治疗抑郁症的一种有前景的额外选择。
