Antibodies to retroviruses in recent onset psychosis and multi-episode schizophrenia

Background: Immunological abnormalities involving the upregulation of endogenous retroviruses have been associated with schizophrenia in small studies.

Methods: Blood samples from 666 individuals (163 with recent onset psychosis, 268 with multi-episode schizophrenia, and 235 controls) were assayed for IgG antibodies to murine leukemia virus (MuLV), Mason-Pfizer monkey virus (MPMV), and feline immunodeficiency virus (FIV) by enzyme immunoassay utilizing whole virus and viral components. Antibody levels in the psychiatric groups were compared to controls by multivariate linear regression. Odds ratios associated with increased antibody levels were calculated based on values ≥ 75th percentile of the controls. Samples were also tested for antibodies to viral proteins by Western blotting and for DNA from infectious retroviruses by real time PCR. Homology between the target virus and the prototype human genome was determined using sequence analysis methods.

Results: Compared with controls, individuals with recent onset of psychosis had increased levels of antibodies to MPMV and MuLV (both p<.001 adjusted for covariates), and increased antibody levels for defined portions of the MPMV and MuLV gag, pol and env proteins. The specificity of these antibodies was confirmed by Western blotting. Individuals with multi-episode schizophrenia did not show elevated antibody levels to any of the retroviruses measured. Infectious retroviruses were not detected in the blood of any participants. Homology analyses indicated that there are multiple regions of the human genome homologous with MPMV and MuLV proteins, the highest being with the MuLV gag protein.

Conclusions: Antibodies to retroviral proteins are elevated in individuals with recent onset psychosis but not in individuals with multi-episode schizophrenia. The immunopathological consequences of this antibody response should be the subject of additional studies.