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Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation
BACKGROUND: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neu...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
CMA Joule Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526153/ https://www.ncbi.nlm.nih.gov/pubmed/34467747 http://dx.doi.org/10.1503/jpn.200166 |
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author | Duan, Jia Wei, Yange Womer, Fay Y. Zhang, Xizhe Chang, Miao Zhu, Yue Liu, Zhuang Li, Chao Yin, Zhiyang Zhang, Ran Sun, Jiaze Wang, Pengshuo Wang, Shuai Jiang, Xiaowei Wei, Shengnan Zhang, Yanbo Tang, Yanqing Wang, Fei |
author_facet | Duan, Jia Wei, Yange Womer, Fay Y. Zhang, Xizhe Chang, Miao Zhu, Yue Liu, Zhuang Li, Chao Yin, Zhiyang Zhang, Ran Sun, Jiaze Wang, Pengshuo Wang, Shuai Jiang, Xiaowei Wei, Shengnan Zhang, Yanbo Tang, Yanqing Wang, Fei |
author_sort | Duan, Jia |
collection | PubMed |
description | BACKGROUND: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter. METHODS: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-β1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function. RESULTS: In the patient group, abnormal white matter was negatively associated with NRG1-β1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-β1 levels and clinical manifestations. LIMITATIONS: Medication status, the wide age range and our cross-sectional findings were limitations of this study. CONCLUSION: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications. |
format | Online Article Text |
id | pubmed-8526153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | CMA Joule Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85261532021-10-22 Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation Duan, Jia Wei, Yange Womer, Fay Y. Zhang, Xizhe Chang, Miao Zhu, Yue Liu, Zhuang Li, Chao Yin, Zhiyang Zhang, Ran Sun, Jiaze Wang, Pengshuo Wang, Shuai Jiang, Xiaowei Wei, Shengnan Zhang, Yanbo Tang, Yanqing Wang, Fei J Psychiatry Neurosci Research Paper BACKGROUND: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter. METHODS: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-β1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function. RESULTS: In the patient group, abnormal white matter was negatively associated with NRG1-β1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-β1 levels and clinical manifestations. LIMITATIONS: Medication status, the wide age range and our cross-sectional findings were limitations of this study. CONCLUSION: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications. CMA Joule Inc. 2021-09-01 /pmc/articles/PMC8526153/ /pubmed/34467747 http://dx.doi.org/10.1503/jpn.200166 Text en © 2021 CMA Joule Inc. or its licensors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Research Paper Duan, Jia Wei, Yange Womer, Fay Y. Zhang, Xizhe Chang, Miao Zhu, Yue Liu, Zhuang Li, Chao Yin, Zhiyang Zhang, Ran Sun, Jiaze Wang, Pengshuo Wang, Shuai Jiang, Xiaowei Wei, Shengnan Zhang, Yanbo Tang, Yanqing Wang, Fei Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title | Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title_full | Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title_fullStr | Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title_full_unstemmed | Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title_short | Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
title_sort | neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526153/ https://www.ncbi.nlm.nih.gov/pubmed/34467747 http://dx.doi.org/10.1503/jpn.200166 |
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