title: Methylation patterns in whole blood correlate with symptoms in schizophrenia patients.
abstract: DNA methylation, one of the main epigenetic mechanisms to regulate gene expression, appears to be involved in the development of schizophrenia (SZ). In this study, we investigated 7562 DNA methylation markers in blood from 98 SZ patients and 108 healthy controls. A linear regression model including age, gender, race, alcohol, nicotine and cannabis use status, and diagnosis was implemented to identify C-phosphate-G (CpG) sites significantly associated with diagnosis. These CpG sites were further validated using an independent data set. Sixteen CpG sites were identified with hyper- or hypomethylation in patients. A further verification of expression of the corresponding genes identified 7 genes whose expression levels were also significantly altered in patients. While such altered methylation patterns showed no correlation with disorganized symptoms and negative symptoms in patients, 11 CpG sites significantly correlated with reality distortion symptoms. The direction of the correlations indicates that methylation changes possibly play a protective mechanism to lessen delusion and hallucination symptoms in patients. Pathway analyses showed that the most significant biological function of the differentially methylated CpGs is inflammatory response with CD224, LAX1, TXK, PRF1, CD7, MPG, and MPO genes directly involved in activations of T cells, B cells, and natural killer cells or in cytotoxic reaction. Our results suggest that such methylation changes may modulate aspects of the immune response and hence protect against the neurobiological substrate of reality distortion symptoms in SZ patients.
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM; jliu@mrn.org.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM;
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany; MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA;
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany; MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA;
authors.forename: Esther
authors.initials: E
authors.lastname: Walton
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus University, Rotterdam, Netherlands;
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM;
authors.forename: Nora
authors.initials: N
authors.lastname: Perrone-Bizzozero
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM.
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Psychiatry, University of New Mexico, Albuquerque, NM.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM; Department of Neurosciences, University of New Mexico, Albuquerque, NM; Department of Psychiatry, University of New Mexico, Albuquerque, NM.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000453:epidemiology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016014:Linear Models; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012565:Schizophrenic Psychology; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
keywords: gene expression; hyper- or hypo; inflammatory response; methylation; reality distortion symptom