title: Results from a hypothesis generating case-control study: herpes family viruses and schizophrenia among military personnel.
abstract: BACKGROUND
  Herpes family viruses can cause central nervous system inflammatory changes that can present with symptoms indistinguishable from schizophrenia and therefore are of interest in schizophrenia research. Most existing studies of herpes viruses have used small populations and postdiagnosis specimens. As part of a larger research program, we conducted a hypothesis-generating case-control study of selected herpes virus antibodies among individuals discharged from the US military with schizophrenia and pre- and postdiagnosis sera.
  
  
  METHODS
  Cases (n = 180) were servicemembers hospitalized and discharged from military service with schizophrenia. Controls, 3:1 matched on several factors, were members not discharged. The military routinely collects and stores members' serum specimens. We used microplate enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to 6 herpes viruses in pre- and postdiagnosis specimens. Conditional logistic regression was used, and the measure of association was the hazard ratio (HR).
  
  
  RESULTS
  Overall, we found a significant association between human herpes virus type 6 and schizophrenia, with an HR of 1.17 (95% confidence interval [CI] = 1.04, 1.32). Women and blacks had significant negative associations with herpes simplex virus type 2 and cytomegalovirus; among blacks, there was a significant positive association with herpes simplex virus type 1. Among men, there was a HHV-6 temporal effect with an HR of 1.41 (95% CI = 1.02, 1.96) for sera drawn 6-12 months before diagnosis.
  
  
  CONCLUSIONS
  Findings from previous studies of herpes family viruses and schizophrenia have been inconsistent. Our study is based on a larger population than most previous studies and used serum specimens collected before onset of illness. This study adds to the body of knowledge and provides testable hypotheses for follow-on studies.
authors.affiliation: Division of Preventive Medicine, Department of Epidemiology, Walter Reed Army Institute of Research, Silver Spring, MD 20901, USA. David.Niebuhr@na.amedd.army.mil
authors.forename: David W
authors.initials: DW
authors.lastname: Niebuhr
authors.forename: Amy M
authors.initials: AM
authors.lastname: Millikan
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Yuanzhang
authors.initials: Y
authors.lastname: Li
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D044383:Black People / Q000523:psychology / Q000706:statistics & numerical data; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology; D020803:Encephalitis, Herpes Simplex / Q000208:ethnology / Q000276:immunology / Q000523:psychology; D005260:Female; D006564:Herpesviridae / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008889:Military Personnel / Q000523:psychology* / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000208:ethnology / Q000276:immunology* / Q000821:virology; D012737:Sex Factors; D044465:White People / Q000523:psychology / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G