Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
BMC Psychiatry. 2024 Apr 2;24(1):248. doi: 10.1186/s12888-024-05689-0.
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.
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).
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.
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.
谷氨酸能功能异常与治疗抵抗性精神分裂症（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。最近有证据表明，免疫过程和抗神经元抗体的患病率增加与 TRS 有关。本研究旨在调查 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。
采用酶联免疫吸附试验（ELISA）测量和比较氯氮平治疗的 TRS 患者（TRS-C，n=37）、氯氮平未治疗的 TRS 患者（TRS-NC，n=39）和非 TRS 患者（nTRS，n=35）的抗谷氨酸受体抗体（NMDAR、AMPA、mGlur3、mGluR5）水平。采用阳性和阴性症状量表（PANSS）评估临床症状严重程度，采用 MATRICS 共识认知电池（MCCB）评估认知功能。
TRS-NC 中所有四种谷氨酸受体抗体的水平均明显高于 nTRS（p<0.001）和 TRS-C（p<0.001），而 TRS-C 中的抗体水平与 nTRS 相当。然而，在 FDR 校正后，在所有三组中，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相关性。
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，并进一步表明谷氨酸能功能障碍和免疫过程可能参与 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。
