难治性精神分裂症（TRS）患者，特别是对氯氮平（CTRS）耐药的患者，由于对标准抗精神病药物治疗的反应有限而面临临床挑战。肿瘤坏死因子-α (TNF-α)、白细胞介素 2 (IL-2) 和白细胞介素 6 (IL-6) 等炎症因子与精神分裂症的病理生理学有关。我们的研究检查了 TRS 患者的认知功能、精神病理症状和炎症因子，重点关注 CTRS 和非 CTRS 个体以及健康对照之间的差异。招募了 115 名 TRS 患者和 84 名健康对照者，评估 IL-2、IL-6 和 TNF-α。应用阳性和阴性综合征量表（PANSS）评估精神病理症状，而应用可重复电池神经心理状态评估（RBANS）评估认知功能。与非 CTRS 患者相比，CTRS 患者表现出较低的视觉空间结构评分 (p = 0.015)、较高的 PANSS 评分、较高的 IL-2 水平和减少的 TNF-α (p < 0.05)。值得注意的是，IL-2 与 CTRS 患者的精神病理学症状独立相关（Beta= 0.268，t= 2.075，p= 0.042），而 IL-6 与非 CTRS 患者的精神病理学症状相关（Beta=- 0.327，t= - 2.109，p = 0.042）。 CTRS 患者的性别特异性分析显示，IL-2 与女性中 PANSS 总症状和阳性症状相关，TNF-α 与男性中 PANSS 阳性症状相关。此外，IL-2、IL-6和TNF-α在TRS患者和CTRS患者中显示出潜在的诊断价值（p<0.05）。氯氮平耐药症状代表了精神分裂症的一种独立的内表型，具有独特的免疫炎症特征，可能受到性别的影响。© 2024。Springer-Verlag GmbH 德国，Springer Nature 旗下公司。

Patients with treatment-resistant schizophrenia (TRS), particularly those resistant to clozapine (CTRS), pose a clinical challenge due to limited response to standard antipsychotic treatments. Inflammatory factors like tumor necrosis factor-alpha (TNF-α), interleukin 2 (IL-2), and interleukin 6 (IL-6) are implicated in schizophrenia's pathophysiology. Our study examines cognitive function, psychopathological symptoms and inflammatory factors in TRS patients, focusing on differences between CTRS and non-CTRS individuals, as well as healthy controls. A cohort of 115 TRS patients and 84 healthy controls were recruited, assessing IL-2, IL-6 and TNF-α. The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathological symptoms, while the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was applied to assess cognitive functioning. CTRS patients showed lower visuospatial constructional score (p = 0.015), higher PANSS scores, higher levels of IL-2 and reduced TNF-α than non-CTRS patients (p < 0.05). Notably, IL-2 was independently associated with psychopathology symptoms in CTRS patients (Beta = 0.268, t = 2.075, p = 0.042), while IL-6 was associated with psychopathology symptoms in non-CTRS patients (Beta = - 0.327, t = - 2.109, p = 0.042). Sex-specific analysis in CTRS patients revealed IL-2 associations with PANSS total and positive symptoms in females, and TNF-α associations with PANSS positive symptoms in males. Furthermore, IL-2, IL-6, and TNF-α displayed potential diagnostic value in TRS patients and CTRS patients (p < 0.05). Clozapine‑resistant symptoms represent an independent endophenotype in schizophrenia with distinctive immunoinflammatory characteristics, potentially influenced by sex.© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.