1)宁波大学教师教育学院,宁波 315211;2)宁波大学医学部基础医学院,宁波 315211;3)宁波大学附属康宁医院药物临床试验质量管理规范办公室,宁波 315100
宁波市卫生健康科技计划(2024Y17),宁波市自然科学基金公益项目(2022S027)和宁波大学王宽诚幸福基金资助。
1)Collge of Teacher Education, Ningbo University, Ningbo 315211, China;2)Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China;3)Good Clinical Practice Office, The Affiliated Kangning Hospital of Ningbo University,Ningbo 315100, China
This work was supported by grants from the Ningbo Health Science and Technology Program (2024Y17), the Ningbo Natural Science Foundation Public Welfare Project (2022S027), and the K. C. Wong Foundation for Happiness of Ningbo University.
精神分裂症是一种以阳性症状、阴性症状和认知功能损害为核心的重性精神障碍,其中认知损伤严重影响患者的社会功能与预后。尽管抗精神病药物对阳性症状有效,但对认知改善作用有限,且长期使用可能引发代谢综合征等不良反应,因此探索安全有效的非药物治疗成为研究热点。本文系统综述了6种非药物干预策略,认知矫正治疗(CRT)、重复经颅磁刺激(rTMS)、经颅直流电刺激(tDCS)、电针治疗(EA)、有氧运动(AE)和光疗(LT),在改善精神分裂症患者认知功能方面的研究进展与临床证据。CRT通过任务训练增强神经可塑性,改善执行功能和社会认知。rTMS和tDCS通过调节皮层兴奋性和神经网络连接,对工作记忆和注意力具有潜在改善作用。EA结合针灸与电刺激,调节脑源性神经营养因子(BDNF)水平,改善记忆功能,适用于药物难治性患者。AE通过增强海马可塑性改善记忆与注意力,适合作为基础干预。LT在动物模型中显示出良好前景,但临床研究尚处于起步阶段。此外,本文还探讨了联合干预策略及未来个体化治疗、关键期干预和多模态整合的发展趋势,旨在为临床和科研提供系统参考,推动非药物干预在精神分裂症认知康复中的应用与研究。
Schizophrenia is a severe psychiatric disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and cognitive impairments. Among these, cognitive impairment is a core feature that severely compromises patients’ social functioning and long-term prognosis. Antipsychotics, the first-line treatment for schizophrenia, are generally effective in managing positive symptoms. However, their efficacy in alleviating negative symptoms and cognitive deficits remains limited. Moreover, long-term use may lead to metabolic syndrome and extrapyramidal side effects. Consequently, non-pharmacological interventions have garnered increasing attention as alternative or adjunctive strategies for cognitive remediation in schizophrenia. In recent years, techniques grounded in neuroplasticity theory have advanced rapidly. These interventions aim to alleviate cognitive impairments by modulating neural circuits (e.g., enhancing prefrontal-hippocampal connectivity) and synaptic plasticity (e.g., modulating the BDNF/TrkB pathway) from multiple dimensions. Such approaches not only enhance cognitive function but also reduce medication-related adverse effects and improve treatment compliance. This article comprehensively reviews the clinical evidence and recent technological advances in non-pharmacological interventions targeting cognitive impairments in schizophrenia. The interventions discussed include cognitive remediation therapy (CRT), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), electro-acupuncture (EA), aerobic exercise (AE), and light therapy (LT). CRT, the most extensively studied and evidence-based intervention, uses structured cognitive training tasks to enhance neuroplasticity and has consistently demonstrated efficacy in improving executive function and social cognition. Both rTMS and tDCS are non-invasive brain stimulation techniques that modulate cortical excitability and neural network connectivity. While rTMS has shown promise in improving working memory and attention—particularly in patients with prominent negative symptoms—its clinical efficacy remains inconsistent, likely due to variability in stimulation parameters and patient heterogeneity. In contrast, tDCS has demonstrated encouraging effects on working memory and attention with a relatively rapid onset, although optimal stimulation protocols have yet to be standardized. EA, which combines traditional acupuncture with electrical stimulation, has been shown to improve memory function, possibly through upregulation of brain-derived neurotrophic factor (BDNF) and enhanced cerebral blood flow. It may be especially useful in treatment-resistant cases. AE is a low-cost and widely accessible intervention that promotes hippocampal neuroplasticity and BDNF expression, thereby improving memory and attention. It is recommended as a foundational adjunctive therapy, particularly for patients with chronic schizophrenia. LT, although still experimental, has yielded promising results in animal models by modulating neuroinflammation and enhancing neurogenesis via the BDNF/CREB signaling pathway. However, clinical evidence remains limited, necessitating further large-scale trials to validate its efficacy and safety. In addition to reviewing individual interventions, this article highlights the potential of combination strategies—such as CRT combined with AE or rTMS—to produce synergistic cognitive benefits. Future directions include the development of personalized treatment protocols, early intervention during neurodevelopmental windows (e.g., adolescence), and the integration of biomarkers and neuroimaging to guide therapeutic decisions. This synthesis aims to provide clinicians and researchers with a comprehensive framework for advancing non-pharmacological cognitive rehabilitation in schizophrenia.
冯家欣,谢彦鸿,李伊,林佛香,黄敏芳,王钦文,王正春.精神分裂症核心认知损伤的非药物治疗[J].生物化学与生物物理进展,2025,52(11):2772-2787
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