Tabriz University of Medical Sciences BioImpacts 2228-5652 15 1 2025 01 19 A potential mechanism for tau protein modulating in schizophrenia with transcranial direct current stimulation intervention: A randomized controlled trial 30274 30274 10.34172/bi.30274 EN Ali Reza Shafiee-Kandjani https://orcid.org/0000-0002-3045-2644 Farnaz Chalabianloo https://orcid.org/0009-0008-8827-452X Sara Farhang https://orcid.org/0000-0001-8552-138X Dariush Shanehbandi https://orcid.org/0000-0002-9449-0607 Behzad Shalchi https://orcid.org/0000-0001-5918-2919 Journal Article 10.34172/bi.30274 2024 01 16 2024 04 28 Introduction: Schizophrenia involves cognitive deficits, including working memory impairments. Researches indicate tau protein abnormalities may contribute to cognitive dysfunction in schizophrenia. While transcranial direct current stimulation (tDCS) shows promise in improving cognitive function, its effects on tau protein and working memory in schizophrenia remain unclear. Methods: Forty participants were randomly assigned to receive either tDCS or sham treatment in this randomized clinical trial. The tDCS group received anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 minutes, while the sham group received a placebo. Serum tau levels and working memory were assessed before and after using ELISA and the digit span task. Results: The results showed that the tDCS group had a significantly higher increase in phosphorylated tau protein serum levels compared to the sham group (5.53 ± 3.67 vs. 1.49 ± 3.90, P < 0.05). There was no significant mean change difference in serum levels of total tau protein between the groups. Females displayed higher increase in both total tau (1.88 ± 0.66 vs. 1.43 ± 0.80, P = 0.664) and p-tau levels (4.92 ± 0.88 vs. 2.11 ± 0.64, P = 0.014). The tDCS group also showed significantly higher improvement in working memory than the sham group (P < 0.05). Correlations between tau changes and memory enhancements approached significance (r(total tau) = 0.30; P = 0.051, r(p-tau ) = 0.27; P = 0.063). Conclusion: These findings reveal the tDCS impact on tau markers, shedding light on the disorder's molecular pathways and sex influences. Enhanced memory, linked to tau changes, suggests its potential as a treatment indicator.