Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia
Abstract Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | npj Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-021-00164-1 |
| _version_ | 1827614965730639872 |
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| author | Bao-Yu Chen Jin-Jia Lin Ming-Kun Lu Hung-Pin Tan Fong-Lin Jang Sheng-Hsiang Lin |
| author_facet | Bao-Yu Chen Jin-Jia Lin Ming-Kun Lu Hung-Pin Tan Fong-Lin Jang Sheng-Hsiang Lin |
| author_sort | Bao-Yu Chen |
| collection | DOAJ |
| description | Abstract Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) are neurological abnormalities that may be intermediate phenotypes or endophenotypes for schizophrenia. Our previous study found poorer performance on NSS tests from patients with EOS and their unaffected first-degree relatives. Thus, we aimed to identify a set of aberrant neurodevelopmental-related miRNAs that could serve as potential biomarkers for EOS or schizophrenia with NSS. This study included 215 schizophrenia patients (104 EOS and 111 AOS), 72 unaffected first-degree relatives, 31 patients with bipolar disorder, and 100 healthy controls. Differential expression analysis revealed that miR-137, miR-34b, and miR-34c were significantly up-regulated in patients with schizophrenia and their unaffected first-degree relatives compared to healthy controls. Receiver operating characteristic (ROC) analysis showed that the miR-137 expression signature could be used to discriminate between patients with EOS and healthy controls (AUC = 0.911). Additionally, miR-34b had the highest ability to discriminate between EOS and AOS (AUC = 0.810), which may indicate different aetiological pathways to disease onset. Moreover, miR-137 dysregulation was correlated with almost all NSS subscales (i.e., sensory integration, motor sequencing, etc.) and, when EOS patients with NSS, miR-137 expression discriminated these patients from healthy controls to a greater extent (AUC = 0.957). These findings support the potential for neurodevelopmental-related miRNAs to be used as indicators of vulnerability to EOS. |
| first_indexed | 2024-03-09T09:02:27Z |
| format | Article |
| id | doaj.art-af5f35c8f9da41ce8df26dfab4c34c08 |
| institution | Directory Open Access Journal |
| issn | 2334-265X |
| language | English |
| last_indexed | 2024-03-09T09:02:27Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Schizophrenia |
| spelling | doaj.art-af5f35c8f9da41ce8df26dfab4c34c082023-12-02T11:14:24ZengNature Portfolionpj Schizophrenia2334-265X2021-07-01711910.1038/s41537-021-00164-1Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophreniaBao-Yu Chen0Jin-Jia Lin1Ming-Kun Lu2Hung-Pin Tan3Fong-Lin Jang4Sheng-Hsiang Lin5Institute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of Psychiatry, Chi Mei Medical CenterDepartment of Health, Jianan Mental HospitalDepartment of Health, Jianan Mental HospitalDepartment of Psychiatry, Chi Mei Medical CenterInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityAbstract Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) are neurological abnormalities that may be intermediate phenotypes or endophenotypes for schizophrenia. Our previous study found poorer performance on NSS tests from patients with EOS and their unaffected first-degree relatives. Thus, we aimed to identify a set of aberrant neurodevelopmental-related miRNAs that could serve as potential biomarkers for EOS or schizophrenia with NSS. This study included 215 schizophrenia patients (104 EOS and 111 AOS), 72 unaffected first-degree relatives, 31 patients with bipolar disorder, and 100 healthy controls. Differential expression analysis revealed that miR-137, miR-34b, and miR-34c were significantly up-regulated in patients with schizophrenia and their unaffected first-degree relatives compared to healthy controls. Receiver operating characteristic (ROC) analysis showed that the miR-137 expression signature could be used to discriminate between patients with EOS and healthy controls (AUC = 0.911). Additionally, miR-34b had the highest ability to discriminate between EOS and AOS (AUC = 0.810), which may indicate different aetiological pathways to disease onset. Moreover, miR-137 dysregulation was correlated with almost all NSS subscales (i.e., sensory integration, motor sequencing, etc.) and, when EOS patients with NSS, miR-137 expression discriminated these patients from healthy controls to a greater extent (AUC = 0.957). These findings support the potential for neurodevelopmental-related miRNAs to be used as indicators of vulnerability to EOS.https://doi.org/10.1038/s41537-021-00164-1 |
| spellingShingle | Bao-Yu Chen Jin-Jia Lin Ming-Kun Lu Hung-Pin Tan Fong-Lin Jang Sheng-Hsiang Lin Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia npj Schizophrenia |
| title | Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia |
| title_full | Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia |
| title_fullStr | Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia |
| title_full_unstemmed | Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia |
| title_short | Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia |
| title_sort | neurodevelopment regulators mir 137 and mir 34 family as biomarkers for early and adult onset schizophrenia |
| url | https://doi.org/10.1038/s41537-021-00164-1 |
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