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Schizophrenia Bulletin Advance Access published online on December 21, 2007

Schizophrenia Bulletin, doi:10.1093/schbul/sbm139
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© The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel

David W. Niebuhr1,2, Amy M. Millikan2, Robert Yolken3, Yuanzhang Li2 and Natalya S. Weber2
2 Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD
3 Johns Hopkins University School of Medicine, Baltimore, MD

1 To whom correspondence should be addressed; Department of Epidemiology, Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD 20901; tel: 301-319-9833, fax: 301-319-9104, e-mail: David.Niebuhr{at}na.amedd.army.mil.

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. Discussion: 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.

Keywords: herpes / virus / schizophrenia / psychosis / antibodies / military


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