Yange WEI, Shanyuan HE, Peng LUO, Rongxun LIU, Hanshuo SU, Zengyuan SHEN, Shuqi FENG, Yanran WU, Guangjun JI, Wei ZHENG, Fei WANG, Chuansheng WANG
Alpha Psychiatry - 2026;27(1):46768-46768
Background: Schizophrenia primarily depends on pharmacotherapy, which has demonstrated limited efficacy in enhancing cognitive impairments. High-definition transcranial direct current stimulation (HD-tDCS) and computerized cognitive remediation therapy (CCRT) hold potential for improving cognitive impairments. This study aims to investigate the effects of combining HD-tDCS with CCRT on cognition and to explore the mechanisms of this approach in schizophrenia. Study Design: This is the protocol of a randomized controlled trial. Methods: Schizophrenia patients will be randomly assigned to one of 4 groups: HD-tDCS + CCRT group (Group 1), HD-tDCS group (Group 2), CCRT group (Group 3), and a control group (Group 4). The central electrode will be personalized using magnetic resonance imaging (MRI)-guided localization in the medial prefrontal cortex (mPFC). CCRT includes 6 therapeutic modules and 10 distinct tasks. Both HD-tDCS and CCRT will be administered once daily, 5 days per week, for 4 consecutive weeks, culminating in a total of 20 sessions. Assessments will occur at baseline (T0), after 10 sessions (T1), after 20 sessions (T2), and after 6 months of follow-up (T3). The primary outcome measure is the change in cognition. We will employ multimodal MRI, serum concentrations of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to explore the underlying mechanisms. Expected Results: An involvement of mPFC and synaptic plasticity in response to HD-tDCS and CCRT is hypothesized. Conclusion: The study will provide empirical evidence for the effectiveness of combined therapy at an individual level, explore its mechanisms, and may ultimately result in personalized medicine. Clinical Trial Registration: ChiCTR2500102731, https://www.chictr.org.cn/hvshowprojectEN.html?id=276964&v=1.0.
