ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Molecular Psychiatry
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1574391
Association between GRIN2B DNA methylation and cognitive impairment: a cross-sectional study of patients with bipolar depression
Provisionally accepted- People's Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
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Background: Cognitive impairment is a prevalent feature throughout the course of bipolar disorder (BD) and may contribute to recurrent episodes and poor prognosis. Despite its significant clinical impact, the biological mechanisms underlying cognitive impairment in BD remain poorly understood, complicating treatment efforts. The NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor, encoded by the GRIN2B gene, plays a critical role in cognitive functions.Methods: In this study, we measured the methylation levels of the promoter region of the GRIN2B gene in peripheral blood samples from patients with bipolar depression and healthy controls using the MassARRAY method. Cognitive performance was assessed through a series of standardized neuropsychological tests. Subsequently, we analyzed the correlation between GRIN2B gene promoter methylation levels and cognitive performance in patients with bipolar depression.Results: We identified aberrant methylation levels at multiple CpG sites within the GRIN2B gene promoter region in patients with bipolar depression compared to healthy controls. These methylation changes were significantly associated with impairments in several cognitive domains, including attention and executive function, even after adjusting for potential confounding factors. These findings suggest that aberrant methylation in the GRIN2B gene promoter region may play a critical role in cognitive impairment in bipolar depression.Conclusions: DNA methylation levels in the GRIN2B gene promoter region may represent a potential therapeutic target for addressing cognitive impairment in bipolar depression. These findings provide a theoretical foundation for future clinical diagnosis and the development of targeted treatment strategies.
Keywords: Bipolar Disorder, Depresssion, DNA Methylation, Grin2b, Cognitive impraiment
Received: 10 Feb 2025; Accepted: 25 Apr 2025.
Copyright: © 2025 Yu, Wang, Wu, He and Shaohong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hao Yu, People's Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
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