TY - JOUR
T1 - Neurobiological substrates of major psychiatry disorders
T2 - transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation
AU - Duan, Jia
AU - Wei, Yange
AU - Womer, Fay Y.
AU - Zhang, Xizhe
AU - Chang, Miao
AU - Zhu, Yue
AU - Liu, Zhuang
AU - Li, Chao
AU - Yin, Zhiyang
AU - Zhang, Ran
AU - Sun, Jiaze
AU - Wang, Pengshuo
AU - Wang, Shuai
AU - Jiang, Xiaowei
AU - Wei, Shengnan
AU - Zhang, Yanbo
AU - Tang, Yanqing
AU - Wang, Fei
N1 - Publisher Copyright:
© 2021 CMA Joule Inc. or its licensors.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115278630&partnerID=8YFLogxK
U2 - 10.1503/jpn.200166
DO - 10.1503/jpn.200166
M3 - Article
C2 - 34467747
AN - SCOPUS:85115278630
SN - 1180-4882
VL - 46
SP - E506-E515
JO - Journal of psychiatry & neuroscience : JPN
JF - Journal of psychiatry & neuroscience : JPN
IS - 5
ER -