title: Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel.
abstract: BACKGROUND
  Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways.
  
  
  METHODS
  We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls.
  
  
  RESULTS
  Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR=1.08, p=0.06). Study participants with higher cytomegalovirus (CMV) IgG antibody levels had a reduced risk of developing schizophrenia (HR=0.90; p=0.02). While IgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia.
  
  
  CONCLUSIONS
  Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious/food antigens might be an indicator of an altered immune response to antigenic stimuli.
authors.affiliation: Preventive Medicine Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910, United States.
authors.forename: Yuanzhang
authors.initials: Y
authors.lastname: Li
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Weber
authors.forename: Jared A
authors.initials: JA
authors.lastname: Fisher
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.forename: David N
authors.initials: DN
authors.lastname: Cowan
authors.forename: Rakel A
authors.initials: RA
authors.lastname: Larsen
authors.forename: David W
authors.initials: DW
authors.lastname: Niebuhr
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D005502:Food; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008889:Military Personnel; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012559:Schizophrenia / Q000276:immunology*; D014481:United States; D055815:Young Adult
chemical_list: D000906:Antibodies; D000956:Antigens, Viral
keywords: Biomarker; Case–control; Immune response; Psychosis; Sero-epidemiology