Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
Schizophr Res. 2022 Oct;248:263-270. doi: 10.1016/j.schres.2022.09.022. Epub 2022 Sep 14.
Cognitive impairments, the main determinants of functional outcomes in schizophrenia, had limited treatment responses and need a better understanding of the mechanisms. Dysfunctions of the dopamine system and N-methyl-d-aspartate receptor (NMDAR), the primary pathophysiologies of schizophrenia, may impair cognition. This study explored the effects and interactions of striatal dopamine transporter (DAT) and plasma NMDAR-related amino acids on cognitive impairments in schizophrenia.
We recruited 36 schizophrenia patients and 36 age- and sex-matched healthy controls (HC). All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT and ultra-performance liquid chromatography were applied to determine DAT availability and plasma concentrations of eight amino acids, respectively.
Compared with HC, schizophrenia patients had lower cognitive performance, higher methionine concentrations, decreased concentrations of glutamic acid, cysteine, aspartic acid, arginine, the ratio of glutamic acid to gamma-aminobutyric acid (Glu/GABA), and DAT availability in the left caudate nucleus (CN) and putamen. Regarding memory scores, Glu/GABA and the DAT availability in left CN and putamen exhibited positive relationships, while methionine concentrations showed negative associations in all participants. The DAT availability in left CN mediated the methionine-memory relationship. An exploratory backward stepwise regression analysis for the four biological markers associated with memory indicated that DAT availability in left CN and Glu/GABA remained in the final model.
This study demonstrated the interactions of striatal DAT and NMDAR-related amino acids on cognitive impairments in schizophrenia. Future studies to comprehensively evaluate their complex interactions and treatment implications are warranted.
认知障碍是精神分裂症功能结果的主要决定因素，其治疗反应有限，需要更好地了解其机制。多巴胺系统和 N-甲基-D-天冬氨酸受体（NMDAR）功能障碍是精神分裂症的主要病理生理学改变，可能会损害认知功能。本研究探讨了纹状体多巴胺转运体（DAT）和血浆 NMDAR 相关氨基酸对精神分裂症认知障碍的影响及其相互作用。
我们招募了 36 名精神分裂症患者和 36 名年龄和性别匹配的健康对照者（HC）。所有参与者均接受了注意力、记忆和执行功能的认知评估。应用 99mTc-TRODAT 单光子发射计算机断层扫描和超高效液相色谱法分别测定 DAT 可用性和血浆中 8 种氨基酸的浓度。
与 HC 相比，精神分裂症患者的认知表现较低，蛋氨酸浓度较高，谷氨酸、半胱氨酸、天冬氨酸、精氨酸浓度降低，谷氨酸与γ-氨基丁酸（Glu/GABA）的比值以及左侧尾状核（CN）和壳核的 DAT 可用性降低。在记忆评分方面，Glu/GABA 与左侧 CN 和壳核的 DAT 可用性呈正相关，而蛋氨酸浓度在所有参与者中呈负相关。左侧 CN 的 DAT 可用性介导了蛋氨酸与记忆的关系。对与记忆相关的四个生物标志物进行的探索性向后逐步回归分析表明，左侧 CN 的 DAT 可用性和 Glu/GABA 仍保留在最终模型中。
本研究表明，纹状体 DAT 和 NMDAR 相关氨基酸在精神分裂症认知障碍中存在相互作用。未来需要进一步研究以全面评估它们之间的复杂相互作用及其治疗意义。
