Non-Pharmacological Treatments for Core Cognitive Impairment in Schizophrenia
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1.Collge Of Teacher Education Ningbo University;2.Basic Medical Sciences,Health Science Center,Ningbo University;3.The Affiliated Kangning Hospital of Ningbo University;4.Collge Of Teacher Education Ningbo University, Basic Medical Sciences,Health Science Center,Ningbo University

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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.

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    Abstract:

    Schizophrenia is a severe psychiatric disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and cognitive impairments. Cognitive impairment is a core symptom of patients with schizophrenia, severely impairing their social function and long-term prognosis. Antipsychotics, the first-line treatment for schizophrenia, effectively manage positive symptoms in most patients. However, their efficacy in alleviating negative and cognitive deficits is limited. Moreover, long-term use may lead to syndrome and extrapyramidal side effects. Consequently, non-pharmacological interventions have gained significant attention as alternative or adjunctive strategies for cognitive remediation in schizophrenia. In recent years, non-pharmacological intervention techniques grounded in neuroplasticity theory have developed rapidly. These techniques provide new perspectives for alleviating cognitive impairment in schizophrenia by regulating neural circuits (e.g., enhancing prefrontal-hippocampal connection function) and synaptic plasticity (e.g., modulating the BDNF/TrkB pathway) from multiple dimensions. These novel interventions not only enhance cognitive function but also mitigate medication-related adverse effects and improve patient treatment compliance. This article comprehensively reviews the clinical evidence and technical advancements of non-pharmacological interventions for treating cognitive impairments in schizophrenia, the interventions covered 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, employs 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 potential in enhancing working memory and attention, especially in patients with prominent negative symptoms, its clinical efficacy remains inconsistent across studies, possibly due to variability in stimulation parameters and patient heterogeneity. tDCS, on the other hand, has demonstrated promising effects on working memory and attention, with a relatively rapid onset of action, though optimal protocols are yet to be standardized. EA integrates traditional acupuncture with electrical stimulation and has been shown to improve memory function, likely through upregulation of brain-derived neurotrophic factor (BDNF) and enhancement of cerebral blood flow. It may be particularly beneficial in treatment-resistant cases. AE, a low-cost and accessible intervention, promotes hippocampal neuroplasticity and BDNF expression, leading to improvements in memory and attention. It is recommended as a foundational adjunctive therapy, especially in chronic patients. LT, though still in the experimental stage, has shown promising results in animal models by modulating neuroinflammation and enhancing neurogenesis via the BDNF/CREB signaling pathway. However, clinical evidence remains limited, and further large-scale trials are needed to validate its efficacy and safety. In addition to reviewing individual interventions, the review highlights the potential of combination strategies, such as CRT paired with AE or rTMS, to produce synergistic cognitive benefits. Future directions include personalized treatment protocols, early intervention during neurodevelopmental windows (e.g., adolescence), and the integration of biomarkers and neuroimaging to guide therapy. This synthesis aims to provide clinicians and researchers with a comprehensive framework for advancing non-pharmacological cognitive rehabilitation in schizophrenia.

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Jiaxin Feng, Yanhong Xie, Yi Li, Foxiang Lin, Minfang Huang, Qinwen Wang, Zhengchun Wang. Non-Pharmacological Treatments for Core Cognitive Impairment in Schizophrenia[J]. Progress in Biochemistry and Biophysics,,():

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History
  • Received:April 23,2025
  • Revised:July 17,2025
  • Accepted:July 21,2025
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