气候变化领域集成服务门户(CCPortal): Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia

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DOI	10.1073/pnas.2100032118
	Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia
	Nomoto M.; Konopaske G.T.; Yamashita N.; Aoki R.; Jitsuki-Takahashi A.; Nakamura H.; Makihara H.; Saito M.; Saigusa Y.; Nakamura F.; Watanabe K.; Baba T.; Benes F.M.; Tobe B.T.D.; Pernia C.D.; Coyle J.T.; Sidman R.L.; Hirayasu Y.; Snyder E.Y.; Goshima Y.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: Increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high). © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biomarker; Blood test; Collapsin response mediator protein-2 (crmp2); Cytoskeleton; Dendritic morphology
语种	英语
scopus关键词	biological marker; collapsin response mediator protein-2; nerve protein; signal peptide; gene expression regulation; genetics; genome-wide association study; human; metabolism; nerve cell network; schizophrenia; Biomarkers; Gene Expression Regulation; Genome-Wide Association Study; Humans; Intercellular Signaling Peptides and Proteins; Nerve Net; Nerve Tissue Proteins; Schizophrenia
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251087
作者单位	Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan; Mailman Research Center, Harvard Medical School, McLean Hospital, Belmont, MA 02478, United States; Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030, United States; Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan; Yokohama City University Graduate School of Medicine, Biological Science & Nursing, Yokohama, 236-0004, Japan; Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan; Department of Electrical and Computer Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, 240-8501, Japan; Center for Stem Cells and Regenerative Medicine, Sanford Burnham Prebys Medical...
推荐引用方式 GB/T 7714	Nomoto M.,Konopaske G.T.,Yamashita N.,et al. Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia[J],2021,118(31).
APA	Nomoto M..,Konopaske G.T..,Yamashita N..,Aoki R..,Jitsuki-Takahashi A..,...&Goshima Y..(2021).Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Nomoto M.,et al."Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).