Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States of America; Veterans Affairs Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, United States of America.
Xperimed LLC, Basel, Switzerland; University of Zurich, Zurich, Switzerland.
Schizophr Res. 2023 Aug;258:71-77. doi: 10.1016/j.schres.2023.07.010. Epub 2023 Jul 28.
The negative symptoms of schizophrenia, which often appear earlier than any other symptom, are prominent and clinically relevant in the majority of patients. As a result, interest in their treatment has increased. Patients who exhibit significant negative symptoms have worse functional outcomes than those without, resulting in impairments in occupational, household, and recreational functioning, as well as difficulties in relationships. Yet treatment with currently available medications does not lead to any significant improvements in this core component of schizophrenia. An increased understanding of the pathophysiology underlying negative symptoms and the discovery of novel treatments that do not directly target dopamine offer the potential to develop therapies that may reduce negative symptoms and increase quality of life for patients. The current article will discuss the impact of negative symptoms, outline current measurement tools for the assessment of negative symptoms, and examine how these measures may be improved. Insights into the neural circuitry underlying negative symptoms will be discussed, and promising targets for the development of effective treatments for these symptoms will be identified. As more prospective, large-scale, randomized studies focus on the effects of treatments on negative symptoms, progress in this area is foreseeable. However, improvements in clinical assessment instruments, a better understanding of the underlying neural mechanisms, development of novel treatments with varied targets, and a greater focus on personalized treatment are all important to produce significant benefits for patients with negative symptoms of schizophrenia.
精神分裂症的阴性症状通常比其他任何症状出现得更早,且在大多数患者中表现突出且具有临床意义。因此,人们对其治疗的兴趣有所增加。表现出明显阴性症状的患者比没有阴性症状的患者功能结局更差,导致职业、家庭和娱乐功能受损,以及人际关系困难。然而,目前可用的药物治疗并不能显著改善精神分裂症的这一核心症状。对阴性症状背后的病理生理学有了更深入的了解,以及发现了不直接针对多巴胺的新型治疗方法,为开发可能减轻阴性症状和提高患者生活质量的疗法提供了可能。本文将讨论阴性症状的影响,概述目前用于评估阴性症状的测量工具,并探讨如何改进这些测量工具。还将讨论阴性症状背后的神经回路,并确定开发这些症状有效治疗方法的有前途的靶点。随着更多前瞻性、大规模、随机研究关注治疗对阴性症状的影响,这一领域的进展是可以预见的。然而,改善临床评估工具、更好地理解潜在的神经机制、开发具有不同靶点的新型治疗方法以及更加关注个性化治疗,对于为精神分裂症阴性症状患者带来显著益处都非常重要。