Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Institute of Neuroscience and Medicine 4, INM-4, Forschungszentrum Jülich, Jülich, Germany.
CNS Drugs. 2022 Aug;36(8):819-858. doi: 10.1007/s40263-022-00935-z. Epub 2022 Jul 13.
Cognitive impairments associated with schizophrenia (CIAS) represent a central element of the symptomatology of this severe mental disorder. CIAS substantially determine the disease prognosis and hardly, if at all, respond to treatment with currently available antipsychotics. Remarkably, all drugs presently approved for the treatment of schizophrenia are, to varying degrees, dopamine D/D receptor blockers. In turn, rapidly growing evidence suggests the immense significance of systems other than the dopaminergic system in the genesis of CIAS. Accordingly, current efforts addressing the unmet needs of patients with schizophrenia are primarily based on interventions in other non-dopaminergic systems. In this review article, we provide a brief overview of the available evidence on the importance of specific systems in the development of CIAS. In addition, we describe the promising targets for the development of new drugs that have been used so far. In doing so, we present the most important candidates that have been investigated in the field of the specific systems in recent years and present a summary of the results available at the time of drafting this review (May 2022), as well as the currently ongoing studies.
与精神分裂症相关的认知障碍（CIAS）是这种严重精神障碍症状的核心要素。CIAS 极大地决定了疾病的预后，并且几乎不会（如果有的话）对目前可用的抗精神病药物治疗产生反应。值得注意的是，目前批准用于治疗精神分裂症的所有药物在不同程度上都是多巴胺 D2/D3 受体阻滞剂。反过来，越来越多的证据表明，除了多巴胺能系统之外，其他系统在 CIAS 的发生中具有巨大的意义。因此，目前针对精神分裂症患者未满足需求的努力主要基于对其他非多巴胺能系统的干预。在这篇综述文章中，我们简要概述了现有证据表明特定系统在 CIAS 发展中的重要性。此外，我们描述了迄今为止用于开发新药的有前途的靶点。在这样做的过程中，我们介绍了近年来在特定系统领域中研究最多的最重要候选者，并总结了撰写本综述时（2022 年 5 月）可用的结果以及目前正在进行的研究。
