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FasL、BDNF和IL-1β作为精神分裂症治疗反应预测指标的预后价值

Prognostic Value of FasL, BDNF, and IL-1β as Predictors of Therapeutic Response in Schizophrenia.

作者信息

Szymona-Kuciewicz Zofia, Owe-Larsson Maja, Flis Marta, Karakula-Juchnowicz Hanna, Zdzisinska Barbara, Dudzinska Ewa, Urbanska Ewa M, Szymona Kinga

机构信息

Collegium Medicum, Cardinal Stefan Wyszynski University in Warsaw, Woycickiego 1/3, 01-938 Warsaw, Poland.

Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland.

出版信息

J Clin Med. 2025 Sep 11;14(18):6417. doi: 10.3390/jcm14186417.

Abstract

: Pro-inflammatory, neurotrophic, and proapoptotic factors affect the course of schizophrenia; however, their impact on the clinical response during relapse is not well recognized. A member of TNF family, Fas ligand (FasL), participates in apoptosis, but its connection with treatment-resistant schizophrenia is unknown. : For this preliminary exploratory study, 53 patients with schizophrenia relapse and 45 healthy subjects were enrolled. Pro-inflammatory interleukin IL-1β, brain-derived neurotrophic factor (BDNF), FasL levels, and clinical evaluations (PANSS, SANS, SAPS) were studied at admission, after a 4-week therapy, and at remission. : In the clozapine-treated therapy-resistant group, IL-1β correlated negatively with clinical improvement (admission, 4-week treatment). In patients not treated with clozapine, IL-1β correlated negatively with disease duration (admission). A negative correlation occurred between FasL and clinical improvement in general symptoms (admission, 4-week treatment), FasL and leukocyte count (admission), and IL-1β and BDNF levels (4-week treatment). In the clozapine-treated group, the negative correlation between FasL levels and the leukocyte count was absent. : The severity of psychopathology in patients with schizophrenia seems to correlate with higher IL-1β and lower BDNF. The novelty of our findings is the observation that higher FasL is negatively associated with the degree of clinical improvement. Thus, a decline of FasL during treatment may be proposed as a predictor of clinical recovery. With caution, we suggest that clozapine use may be linked to a protective effect against FasL signaling and the alleviation of apoptotic processes.

摘要

促炎、神经营养和促凋亡因子会影响精神分裂症的病程;然而,它们在复发期间对临床反应的影响尚未得到充分认识。肿瘤坏死因子家族成员Fas配体(FasL)参与细胞凋亡,但其与难治性精神分裂症的关联尚不清楚。

在这项初步探索性研究中,招募了53例精神分裂症复发患者和45名健康受试者。在入院时、4周治疗后及缓解期,研究了促炎白细胞介素IL-1β、脑源性神经营养因子(BDNF)、FasL水平及临床评估指标(阳性和阴性症状量表、阴性症状评定量表、阳性症状评定量表)。

在接受氯氮平治疗的难治性组中,IL-1β与临床改善情况呈负相关(入院时、4周治疗后)。在未接受氯氮平治疗的患者中,IL-1β与病程呈负相关(入院时)。FasL与总体症状的临床改善情况呈负相关(入院时、4周治疗后),FasL与白细胞计数呈负相关(入院时),IL-1β与BDNF水平呈负相关(4周治疗后)。在氯氮平治疗组中,FasL水平与白细胞计数之间不存在负相关。

精神分裂症患者的精神病理学严重程度似乎与较高的IL-1β和较低的BDNF相关。我们研究结果的新颖之处在于观察到较高的FasL与临床改善程度呈负相关。因此,治疗期间FasL的下降可被视为临床康复的预测指标。我们谨慎地提出,使用氯氮平可能与对FasL信号传导的保护作用及凋亡过程的缓解有关。

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