TY - JOUR T1 - Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation JF - Journal of Psychiatry and Neuroscience JO - JPN SP - E506 LP - E515 DO - 10.1503/jpn.200166 VL - 46 IS - 5 AU - Jia Duan AU - Yange Wei AU - Fay Y. Womer AU - Xizhe Zhang AU - Miao Chang AU - Yue Zhu AU - Zhuang Liu AU - Chao Li AU - Zhiyang Yin AU - Ran Zhang AU - Jiaze Sun AU - Pengshuo Wang AU - Shuai Wang AU - Xiaowei Jiang AU - Shengnan Wei AU - Yanbo Zhang AU - Yanqing Tang AU - Fei Wang Y1 - 2021/09/01 UR - http://jpn.ca/content/46/5/E506.abstract 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. ER -