PDF(Pubmed)
Abstract：
BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels.
METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).
RESULTS: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.
CONCLUSIONS: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.
METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).
RESULTS: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.
CONCLUSIONS: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.
摘要：
背景：谷氨酸能功能异常与难治性精神分裂症（TRS）的病因有关，氯氮平的疗效可能归因于其对谷氨酸系统的影响。最近,已经出现的证据表明TRS中免疫过程的参与和抗神经元抗体的患病率增加.本研究旨在研究TRS中多种抗谷氨酸受体抗体的水平，并探讨氯氮平对这些抗体水平的影响。
方法：使用酶联免疫吸附测定（ELISA）来测量和比较抗谷氨酸受体抗体的水平（NMDAR，AMPAR,mGlur3，mGluR5）在氯氮平治疗的TRS患者中（TRS-C，n=37),氯氮平初治TRS患者(TRS-NC，n=39),和非TRS患者(nTRS，n=35)。使用阳性和阴性症状量表（PANSS）评估临床症状严重程度，而使用MATRICS共识认知电池（MCCB）评估认知功能。
结果：TRS-NC中所有四种谷氨酸受体抗体的水平均显着高于nTRS（p<0.001）和TRS-C（p<0.001），TRS-C中的抗体水平与nTRS中的抗体水平相当。然而,在FDR校正后的所有三组中,抗体水平与症状严重程度或认知功能之间均未观察到显著关联.
结论：我们的研究结果表明，TRS可能与抗谷氨酸受体抗体水平升高有关，并进一步证明谷氨酸能功能障碍和免疫过程可能参与了TRS的发病机制。氯氮平对抗谷氨酸受体抗体水平的影响可能是其治疗作用的药理学机制。
方法：使用酶联免疫吸附测定（ELISA）来测量和比较抗谷氨酸受体抗体的水平（NMDAR，AMPAR,mGlur3，mGluR5）在氯氮平治疗的TRS患者中（TRS-C，n=37),氯氮平初治TRS患者(TRS-NC，n=39),和非TRS患者(nTRS，n=35)。使用阳性和阴性症状量表（PANSS）评估临床症状严重程度，而使用MATRICS共识认知电池（MCCB）评估认知功能。
结果：TRS-NC中所有四种谷氨酸受体抗体的水平均显着高于nTRS（p<0.001）和TRS-C（p<0.001），TRS-C中的抗体水平与nTRS中的抗体水平相当。然而,在FDR校正后的所有三组中,抗体水平与症状严重程度或认知功能之间均未观察到显著关联.
结论：我们的研究结果表明，TRS可能与抗谷氨酸受体抗体水平升高有关，并进一步证明谷氨酸能功能障碍和免疫过程可能参与了TRS的发病机制。氯氮平对抗谷氨酸受体抗体水平的影响可能是其治疗作用的药理学机制。
