학술논문
The genome-wide DNA methylation profiles among neurosurgery patients with and without post-operative delirium.
Document Type
Academic Journal
Author
Yamanashi T; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Department of Neuropsychiatry, Tottori University Faculty of Medicine, Tottori, Japan.; Crutchley KJ; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; University of Nebraska Medical Center, Omaha, Nebraska, USA.; Wahba NE; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Nagao T; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Department of Neurosurgery (Sakura), Toho University School of Medicine Faculty of Medicine, Chiba, Japan.; Marra PS; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Akers CC; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Sullivan EJ; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Iwata M; Department of Neuropsychiatry, Tottori University Faculty of Medicine, Tottori, Japan.; Howard MA 3rd; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Cho HR; College of Public Health, University of Iowa, Iowa City, Iowa, USA.; Kawasaki H; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Hughes CG; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Pandharipande PP; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Hefti MM; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.; Shinozaki G; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Source
Publisher: Blackwell Science Country of Publication: Australia NLM ID: 9513551 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1819 (Electronic) Linking ISSN: 13231316 NLM ISO Abbreviation: Psychiatry Clin Neurosci Subsets: MEDLINE
Subject
Language
English
Abstract
Aims: There is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery.
Methods: Pre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted.
Results: When POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as "cellular response to cytokine stimulus", "regulation of immune system process", "regulation of cell activation", and "regulation of cytokine production". Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as "immune response" and "T cell activation", which are same pathways previously identified from an independent non-surgical inpatient cohort.
Conclusions: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics play an important role in the pathophysiological mechanism of delirium and suggest the potential usefulness of an epigenetics-based biomarker of POD.
(© 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)
Methods: Pre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted.
Results: When POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as "cellular response to cytokine stimulus", "regulation of immune system process", "regulation of cell activation", and "regulation of cytokine production". Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as "immune response" and "T cell activation", which are same pathways previously identified from an independent non-surgical inpatient cohort.
Conclusions: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics play an important role in the pathophysiological mechanism of delirium and suggest the potential usefulness of an epigenetics-based biomarker of POD.
(© 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)