Peripheral and central innate immune alterations in schizophrenia and bipolar disorder: a systematic review of NK cells, monocytes and macrophages

Innate immune dysfunction is implicated in schizophrenia (SZ) and bipolar disorder (BD). Alterations in natural killer (NK) cells, monocytes and macrophages occur in both disorders across peripheral and central compartments. This systematic review synthesises current evidence by clinical stage and illness phase. Following PRISMA guidelines, PubMed, Scopus and PsycINFO were searched to May 2025. Eligible studies reported peripheral blood, cerebrospinal fluid (CSF) or post-mortem brain findings. Eighty-one studies met inclusion criteria. In SZ, peripheral data showed altered NK cell subsets and monocyte abnormalities, including elevated counts and inflammatory ratios, particularly in early or acute stages. CSF studies found increased monocyte chemoattractants, and post-mortem analyses revealed macrophage upregulation in frontal and temporal cortices. In BD, NK cell results were limited and inconsistent. Monocyte activation was most evident during symptomatic phases, particularly mania. CSF analyses detected increased monocyte- and macrophage-associated proteins, while post-mortem findings indicated microglial activation in selected cortical and subcortical regions, less consistently than in SZ. Innate immune alterations in SZ and BD partly overlap yet remain disorder- and state-specific. Central compartments and NK cells are underexplored. Stratification by stage and phase may improve interpretability and guide longitudinal, multimodal, cell-specific research for precision immunopsychiatry.

先天免疫功能异常与精神分裂症（SZ）及双相情感障碍（BD）存在密切关联。两类疾病在外周与中枢免疫区域均存在自然杀伤（NK）细胞、单核细胞及巨噬细胞的异常改变。本系统综述依据临床分期与疾病发作阶段，对现有研究证据进行了综合梳理。本研究遵循PRISMA指南，检索了截至2025年5月的PubMed、Scopus及PsycINFO数据库。纳入研究需报告外周血、脑脊液（CSF）或死后脑组织的相关研究结果，最终共有81项研究符合纳入标准。针对精神分裂症，外周血数据分析显示NK细胞亚群异常及单核细胞异常改变，包括单核细胞计数升高与炎症比值上升，此类异常在疾病早期或急性期尤为显著。脑脊液研究发现单核细胞趋化因子水平升高，死后脑组织分析则显示额叶与颞叶皮层的巨噬细胞表达上调。针对双相情感障碍，现有NK细胞相关研究结果有限且结论不一致。单核细胞活化在症状发作期最为明显，尤其在躁狂发作阶段。脑脊液分析检测到单核细胞及巨噬细胞相关蛋白水平升高，死后脑组织研究结果则显示特定皮层与皮层下区域存在小胶质细胞活化，但一致性不及精神分裂症。精神分裂症与双相情感障碍的先天免疫改变存在部分重叠，但仍具有疾病特异性与状态特异性。中枢免疫区域及NK细胞的相关研究仍有待进一步探索。按疾病分期与发作阶段进行分层分析，可提升研究结果的可解释性，同时为精准免疫精神医学领域的纵向、多模态、细胞特异性研究提供指导方向。