Chen X, Zhou YN, Lu XZ, Li RJ, Xiong YF, Sheng X, Zhu WW. Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits. World J Psychiatry 2024; 14(6): 784-793 [PMID: 38984326 DOI: 10.5498/wjp.v14.i6.784]
Corresponding Author of This Article
Wei-Wei Zhu, MM, Associate Chief Physician, Department of Sleep Disorders and Neurosis, Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, No. 427, Section 3, Furong Middle Road, Yuhua District, Changsha 410007, Hunan Province, China. q1640809558@163.com
Research Domain of This Article
Neurosciences
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Xi Chen, Ya-Nan Zhou, Ren-Jiao Li, Xia Sheng, Department of Child and Adolescent Psychiatric, Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, Changsha 410007, Hunan Province, China
Xiao-Zi Lu, Department of Psychiatry, Qingdao Mental Health Center, Qingdao 266034, Shandong Province, China
Yi-Fan Xiong, Department of Psychiatry, Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, Changsha 410007, Hunan Province, China
Wei-Wei Zhu, Department of Sleep Disorders and Neurosis, Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, Changsha 410007, Hunan Province, China
Author contributions: Chen X performed the majority of experiments and wrote the manuscript; Zhou YN and Lu XZ designed the study and corrected the manuscript; Li RJ is involved in analytical tools; Xiong YF and Sheng X participated to the collection of the human material; Zhu WW served as scientific advisor and participate to the collection of human material.
Institutional review board statement: The study was approved by the ethics committee of Brain Hospital of Hunan Province (Approval No. 2023338).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at q1640809558@163.com.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Wei Zhu, MM, Associate Chief Physician, Department of Sleep Disorders and Neurosis, Brain Hospital of Hunan Province, The Second People’s Hospital of Hunan Province, No. 427, Section 3, Furong Middle Road, Yuhua District, Changsha 410007, Hunan Province, China. q1640809558@163.com
Received: March 7, 2024 Revised: April 25, 2024 Accepted: May 10, 2024 Published online: June 19, 2024 Processing time: 104 Days and 4.3 Hours
Abstract
BACKGROUND
The expression pattern of gamma aminobutyric acid (GABA) receptor subunits are commonly altered in patients with schizophrenia, which may lead to nerve excitation/inhibition problems, affecting cognition, emotion, and behavior.
AIM
To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.
METHODS
This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period. The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy. The recognized cognitive battery tool, the MATRICS Consensus Cognitive Battery, was used to evaluate the scores for various dimensions of cognitive function. The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.
RESULTS
Significant differences in GABA receptor subunit levels were found between the case and control groups (P < 0.05). A significant difference was also found between the case and control groups in terms of cognitive function measures, including attention/alertness and learning ability (P < 0.05). Specifically, as the expression levels of GABRA1 (α1 subunit gene), GABRB2 (β2 subunit gene), GABRD (δ subunit), and GABRE (ε subunit) decreased, the severity of the patients’ condition increased gradually, indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia (P < 0.05). However, the expression levels of GABRA5 (α5 subunit gene) and GABRA6 (α6 subunit gene) showed no significant correlation with schizophrenia (P > 0.05).
CONCLUSION
Downregulation of the GABA receptor subunits is positively correlated with schizophrenia. In other words, when GABA receptor subunits are downregulated in patients, cognitive impairment becomes more severe.
Core Tip: The levels of gamma-aminobutyric acid (GABA) receptor subunits differ between the brains of patients with schizophrenia and those of healthy individuals. Patients with schizophrenia show cognitive impairments due to problems with attention, memory, social cognition, and executive functions. Furthermore, downregulation of the GABA receptor subunits GABRA1, GABRB1, GABRD, and GABRE is positively correlated with declining cognitive function in schizophrenia patients. No significant correlation was found between the subunit expression levels of GABRA5 and GABRA6.
