Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis

Abstract Background This study evaluated the utility of serum NR1 and NR2 concentrations in identifying individuals with first-episode schizophrenia (FES) and clinical high risk (CHR) as well as their correlations with clinical symptoms and cognitive domains. Methods This cross-sectional study compa...

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Main Authors: Zhen Mao, Feng Li, Lige Ge, Wenpeng Hou, Yushen Ding, Feifei Wang, Yujie Wen, Xueqi Wang, Yongying Cheng, Weiwei Hou, Lu Wang, Xinke Shi, Qijing Bo, Fang Dong
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06950-w
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author Zhen Mao
Feng Li
Lige Ge
Wenpeng Hou
Yushen Ding
Feifei Wang
Yujie Wen
Xueqi Wang
Yongying Cheng
Weiwei Hou
Lu Wang
Xinke Shi
Qijing Bo
Fang Dong
author_facet Zhen Mao
Feng Li
Lige Ge
Wenpeng Hou
Yushen Ding
Feifei Wang
Yujie Wen
Xueqi Wang
Yongying Cheng
Weiwei Hou
Lu Wang
Xinke Shi
Qijing Bo
Fang Dong
author_sort Zhen Mao
collection DOAJ
description Abstract Background This study evaluated the utility of serum NR1 and NR2 concentrations in identifying individuals with first-episode schizophrenia (FES) and clinical high risk (CHR) as well as their correlations with clinical symptoms and cognitive domains. Methods This cross-sectional study compared peripheral blood NR1 and NR2 concentrations among the FES, CHR, and healthy control (HC) groups and examined their association with cognitive function. Serum concentrations of NR1 and NR2 subunits were measured using ELISA, and cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Concentrations were compared among groups using the analysis of covariance or non-parametric tests and ROC curve analysis, and correlation was determined using the Pearson or Spearman method. Results A total of 41 FES cases, 34 CHR cases, and 41 HC were included in the study. Serum NR1 concentrations significantly varied among the three groups (Z = 16.19, P < 0.001) and were significantly different between the FES group and the CHR (Z = -4.04, P < 0.001) and HC groups (Z = -2.49, P = 0.01). Additionally, serum NR2 concentration was significantly different between the CHR and HC groups (F = 5.37, P = 0.02). In the FES group, serum NR1 concentration was negatively correlated with speed of processing (r = -0.41, P = 0.02), whereas serum NR2 concentration was negatively correlated with verbal learning (r = -0.40, P = 0.02). In the CHR group, serum NR1 concentration was positively correlated with the total MCCB score (r = 0.40, P = 0.04). ROC curve analysis showed that NR2 level was better for discriminating FES (AUC: 69%; sensitivity: 56%; specificity: 85%; optimal cutoff value: 32.80 ng/mL) and CHR (AUC: 74%; sensitivity: 62%; specificity: 85%; optimal cutoff value: 32.77 ng/mL). Conclusions Serum NR1 and NR2 concentrations show potential for early identification of individuals with psychosis, but further validation is needed, and they are also correlated with cognition. Furthermore, serum NR2 concentration is more stable and serves as a promising objective biomarker for quantitative assessment.
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spelling doaj-art-b02e8fc4201445a29a27be72c64aa4152025-08-20T03:48:02ZengBMCBMC Psychiatry1471-244X2025-05-012511910.1186/s12888-025-06950-wSerum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosisZhen Mao0Feng Li1Lige Ge2Wenpeng Hou3Yushen Ding4Feifei Wang5Yujie Wen6Xueqi Wang7Yongying Cheng8Weiwei Hou9Lu Wang10Xinke Shi11Qijing Bo12Fang Dong13The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityBeijing Haidian District Psychological Rehabilitation HospitalThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityAbstract Background This study evaluated the utility of serum NR1 and NR2 concentrations in identifying individuals with first-episode schizophrenia (FES) and clinical high risk (CHR) as well as their correlations with clinical symptoms and cognitive domains. Methods This cross-sectional study compared peripheral blood NR1 and NR2 concentrations among the FES, CHR, and healthy control (HC) groups and examined their association with cognitive function. Serum concentrations of NR1 and NR2 subunits were measured using ELISA, and cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Concentrations were compared among groups using the analysis of covariance or non-parametric tests and ROC curve analysis, and correlation was determined using the Pearson or Spearman method. Results A total of 41 FES cases, 34 CHR cases, and 41 HC were included in the study. Serum NR1 concentrations significantly varied among the three groups (Z = 16.19, P < 0.001) and were significantly different between the FES group and the CHR (Z = -4.04, P < 0.001) and HC groups (Z = -2.49, P = 0.01). Additionally, serum NR2 concentration was significantly different between the CHR and HC groups (F = 5.37, P = 0.02). In the FES group, serum NR1 concentration was negatively correlated with speed of processing (r = -0.41, P = 0.02), whereas serum NR2 concentration was negatively correlated with verbal learning (r = -0.40, P = 0.02). In the CHR group, serum NR1 concentration was positively correlated with the total MCCB score (r = 0.40, P = 0.04). ROC curve analysis showed that NR2 level was better for discriminating FES (AUC: 69%; sensitivity: 56%; specificity: 85%; optimal cutoff value: 32.80 ng/mL) and CHR (AUC: 74%; sensitivity: 62%; specificity: 85%; optimal cutoff value: 32.77 ng/mL). Conclusions Serum NR1 and NR2 concentrations show potential for early identification of individuals with psychosis, but further validation is needed, and they are also correlated with cognition. Furthermore, serum NR2 concentration is more stable and serves as a promising objective biomarker for quantitative assessment.https://doi.org/10.1186/s12888-025-06950-wNR1NR2First-episode schizophreniaClinical high risk
spellingShingle Zhen Mao
Feng Li
Lige Ge
Wenpeng Hou
Yushen Ding
Feifei Wang
Yujie Wen
Xueqi Wang
Yongying Cheng
Weiwei Hou
Lu Wang
Xinke Shi
Qijing Bo
Fang Dong
Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
BMC Psychiatry
NR1
NR2
First-episode schizophrenia
Clinical high risk
title Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
title_full Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
title_fullStr Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
title_full_unstemmed Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
title_short Serum NR1 and NR2 concentrations in first-episode schizophrenia and clinical high-risk for psychosis
title_sort serum nr1 and nr2 concentrations in first episode schizophrenia and clinical high risk for psychosis
topic NR1
NR2
First-episode schizophrenia
Clinical high risk
url https://doi.org/10.1186/s12888-025-06950-w
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