Yang Kai-Chun, Yang Bang-Hung, Lan Chen-Chia, Liu Mu-N, Chou Yuan-Hwa
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Psychol Med. 2024 Dec 2;54(15):1-11. doi: 10.1017/S0033291724002228.
Cognitive impairment, a major determinant of poor functioning in schizophrenia, had limited responses to existing antipsychotic drugs. The limited efficacy could be due to regional differences in the dysregulation of the dopamine system. This study investigated striatal and peripheral dopaminergic makers in schizophrenia and their relationship with cognitive impairment.
Thirty-three patients with schizophrenia and 36 age- and sex-matched healthy controls (HC) participated. We evaluated their cognitive performance, examined the availability of striatal dopamine transporter (DAT) using single-photon emission computed tomography with 99mTc-TRODAT, and measured plasma levels of dopaminergic precursors (phenylalanine and tyrosine) and three branched-chain amino acids (BCAA) that compete with precursors for brain uptake via ultra-performance liquid chromatography.
Schizophrenia patients exhibited lower cognitive performance, decreased striatal DAT availability, and reduced levels of phenylalanine, tyrosine, leucine, and isoleucine, and the ratio of phenylalanine plus tyrosine to BCAA. Within the patient group, lower DAT availability in the left caudate nucleus (CN) or putamen was positively associated with attention deficits. Meanwhile, lower tyrosine levels and the ratio of phenylalanine plus tyrosine to BCAA were positively related to executive dysfunction. Among all participants, DAT availability in the right CN or putamen was positively related to memory function, and plasma phenylalanine level was positively associated with executive function.
This study supports the role of dopamine system abnormalities in cognitive impairment in schizophrenia. The distinct associations between different dopaminergic alterations and specific cognitive domain impairments suggest the potential need for multifaceted treatment approaches to target these impairments.
认知障碍是精神分裂症功能不良的主要决定因素，对现有的抗精神病药物反应有限。疗效有限可能是由于多巴胺系统失调的区域差异。本研究调查了精神分裂症患者纹状体和外周多巴胺能标志物及其与认知障碍的关系。
33例精神分裂症患者和36例年龄及性别匹配的健康对照者参与研究。我们评估了他们的认知表现，使用99mTc-TRODAT单光子发射计算机断层扫描检查纹状体多巴胺转运体（DAT）的可用性，并通过超高效液相色谱法测量多巴胺能前体（苯丙氨酸和酪氨酸）以及三种与前体竞争脑摄取的支链氨基酸（BCAA）的血浆水平。
精神分裂症患者表现出较低的认知表现、纹状体DAT可用性降低、苯丙氨酸、酪氨酸、亮氨酸和异亮氨酸水平降低，以及苯丙氨酸加酪氨酸与BCAA的比率降低。在患者组中，左侧尾状核（CN）或壳核中较低的DAT可用性与注意力缺陷呈正相关。同时，较低的酪氨酸水平以及苯丙氨酸加酪氨酸与BCAA的比率与执行功能障碍呈正相关。在所有参与者中，右侧CN或壳核中的DAT可用性与记忆功能呈正相关，血浆苯丙氨酸水平与执行功能呈正相关。
本研究支持多巴胺系统异常在精神分裂症认知障碍中的作用。不同多巴胺能改变与特定认知领域损害之间的明显关联表明，可能需要多方面的治疗方法来针对这些损害。
