N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia

Authors

• Jinghui Tong
• Kebing Yang
• Wei Li
• Leilei Wang
• Yi Yin
• Yanfang Zhou
• Junchao Huang
• Ping Zhang
• Yanli Zhao
• Song Chen
• Hongzhen Fan
• Yimin Cui
• Xingguang Luo
• Shuping Tan
• Zhiren Wang
• Wei Feng
• Baopeng Tian
• Chiang-Shan R Li
• L Elliot Hong
• Yunlong Tan

Language

English

Publication Date

7-7-2025

Journal

Schizophrenia Bulletin

DOI

10.1093/schbul/sbae180

PMID

39406395

PMCID

PMC12236339

PubMedCentral® Posted Date

10-15-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background and hypothesis: Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia.

Study design: We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay.

Study results: The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference).

Conclusions: Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

Keywords

Humans, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Male, Female, Adult, Sensory Gating, Young Adult, Evoked Potentials, Auditory, Antipsychotic Agents, Autoantibodies, Adolescent, first episode schizophrenia, sensory gating deficits, NMDAR antibody, mediation analysis

Published Open-Access

yes

Recommended Citation

Tong, Jinghui; Yang, Kebing; Li, Wei; et al., "N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia" (2025). Faculty, Staff and Student Publications. 4388.
https://digitalcommons.library.tmc.edu/uthmed_docs/4388