Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia
Objective: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited β-secretase 1 (B...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Comprehensive Psychiatry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0010440X20300183 |
| _version_ | 1828414644294778880 |
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| author | Zhengrong Zhang Yuhong Li Fan He Yonghua Cui Yi Zheng Rena Li |
| author_facet | Zhengrong Zhang Yuhong Li Fan He Yonghua Cui Yi Zheng Rena Li |
| author_sort | Zhengrong Zhang |
| collection | DOAJ |
| description | Objective: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited β-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-β1 (NRG1-β1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. Methods: In this study, we collected plasma and clinical information from 71 young patients (7 ≤ age years ≤20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-β1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-β1 and BACE1 levels. Results: We found that circulating plasma levels of NRG1-β1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-β1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-β1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. Conclusion: Our results suggest that decreased levels of NRG1-β1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS. |
| first_indexed | 2024-12-10T13:30:17Z |
| format | Article |
| id | doaj.art-351da6249afe44bc813e059433dce787 |
| institution | Directory Open Access Journal |
| issn | 0010-440X |
| language | English |
| last_indexed | 2024-12-10T13:30:17Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Comprehensive Psychiatry |
| spelling | doaj.art-351da6249afe44bc813e059433dce7872022-12-22T01:47:00ZengElsevierComprehensive Psychiatry0010-440X2020-07-01100152176Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophreniaZhengrong Zhang0Yuhong Li1Fan He2Yonghua Cui3Yi Zheng4Rena Li5National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, ChinaBeijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, ChinaNational Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, ChinaNational Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, ChinaNational Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Correspondence to: Y. Zheng, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China.National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China; Correspondence to: R. Li, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.Objective: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited β-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-β1 (NRG1-β1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. Methods: In this study, we collected plasma and clinical information from 71 young patients (7 ≤ age years ≤20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-β1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-β1 and BACE1 levels. Results: We found that circulating plasma levels of NRG1-β1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-β1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-β1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. Conclusion: Our results suggest that decreased levels of NRG1-β1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS.http://www.sciencedirect.com/science/article/pii/S0010440X20300183Early-onset schizophreniaNeuregulin1-β1 (NRG1-β1)β-Secretase-1 (BACE1)BiomarkerSex differences |
| spellingShingle | Zhengrong Zhang Yuhong Li Fan He Yonghua Cui Yi Zheng Rena Li Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia Comprehensive Psychiatry Early-onset schizophrenia Neuregulin1-β1 (NRG1-β1) β-Secretase-1 (BACE1) Biomarker Sex differences |
| title | Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia |
| title_full | Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia |
| title_fullStr | Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia |
| title_full_unstemmed | Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia |
| title_short | Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia |
| title_sort | sex differences in circulating neuregulin1 β1 and β secretase 1 expression in childhood onset schizophrenia |
| topic | Early-onset schizophrenia Neuregulin1-β1 (NRG1-β1) β-Secretase-1 (BACE1) Biomarker Sex differences |
| url | http://www.sciencedirect.com/science/article/pii/S0010440X20300183 |
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