Pang Tiffanie Sze Wing, Chun Johnny Siu Wah, Wong Ting Yat, Chu Sin Ting, Ma Chak Fai, Honer William G, Chan Sherry Kit Wa
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Psychology, The Education University of Hong Kong, Hong Kong SAR, China.
Schizophrenia (Heidelb). 2023 Sep 26;9(1):65. doi: 10.1038/s41537-023-00392-7.
This systematic review aimed to review neuroimaging studies comparing clozapine-resistant schizophrenia patients with clozapine-responding patients, and with first-line antipsychotic responding (FLR) patients. A total of 19 studies including 6 longitudinal studies were identified. Imaging techniques comprised computerized tomography (CT, n = 3), structural magnetic resonance imaging (MRI, n = 7), magnetic resonance spectroscopy (MRS, n = 5), functional MRI (n = 1), single-photon emission computerized tomography (SPECT, n = 3) and diffusion tensor imaging (DTI, n = 1). The most consistent finding was hypo-frontality in the clozapine-resistant group compared with the clozapine-responding group with possible differences in frontal-striatal-basal ganglia circuitry as well as the GABA level between the two treatment-resistant groups. Additional statistically significant findings were reported when comparing clozapine-resistant patients with the FLR group, including lower cortical thickness and brain volume of multiple brain regions as well as lower Glx/Cr level in the dorsolateral prefrontal cortex. Both treatment-resistant groups were found to have extensive differences in neurobiological features in comparison with the FLR group. Overall results suggested treatment-resistant schizophrenia is likely to be a neurobiological distinct type of the illness. Clozapine-resistant and clozapine-responding schizophrenia are likely to have both shared and distinct neurobiological features. However, conclusions from existing studies are limited, and future multi-center collaborative studies are required with a consensus clinical definition of patient samples, multimodal imaging tools, and longitudinal study designs.
本系统评价旨在回顾比较氯氮平抵抗型精神分裂症患者与氯氮平反应型患者以及一线抗精神病药物反应型（FLR）患者的神经影像学研究。共纳入19项研究，其中包括6项纵向研究。成像技术包括计算机断层扫描（CT，n = 3）、结构磁共振成像（MRI，n = 7）、磁共振波谱（MRS，n = 5）、功能磁共振成像（n = 1）、单光子发射计算机断层扫描（SPECT，n = 3）和扩散张量成像（DTI，n = 1）。最一致的发现是，与氯氮平反应型组相比，氯氮平抵抗型组存在额叶功能减退，两个治疗抵抗型组在额叶-纹状体-基底神经节回路以及GABA水平上可能存在差异。在比较氯氮平抵抗型患者与FLR组时，还报告了其他具有统计学意义的发现，包括多个脑区的皮质厚度和脑容量较低，以及背外侧前额叶皮质的Glx/Cr水平较低。与FLR组相比，两个治疗抵抗型组在神经生物学特征上存在广泛差异。总体结果表明，难治性精神分裂症可能是一种神经生物学上独特的疾病类型。氯氮平抵抗型和氯氮平反应型精神分裂症可能具有共同和独特的神经生物学特征。然而，现有研究的结论有限，未来需要开展多中心协作研究，对患者样本、多模态成像工具和纵向研究设计达成共识的临床定义。
