Neural autoantibodies in psychiatric disorders are associated with antibodies against viral pathogens: a retrospective study of 619 patients

A history of viral infection has been associated with a higher risk for psychiatric disorders. One potential underlying mechanism is that antiviral immunological responses could trigger cross-reactivity between viral and neural antigens, which would raise the co-occurrence of antiviral antibodies and anti-neural autoantibodies. We studied 619 patients' psychiatric diagnoses from the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany. Anti-neural autoantibodies and antiviral antibody specific indices were measured in serum and/or cerebrospinal fluid (CSF) from all patients. Among these 619 patients, 115 tested positive for serum and/or CSF neural autoantibodies (18.6%), with the most often identified autoantibodies being anti-GAD65 in serum (2.2%) and CSF (1.6%), and anti-NMDA in serum (0.6%) and CSF (1.3%). The three main diagnostic groups presenting neural autoantibodies were patients with organic psychiatric disorders including dementia (81 of 377; 21.7%), those with psychotic disorders (9 of 66; 13.6%), and patients with affective disorders (19 of 138; 13.9%). Logistic regression analysis revealed a significant association between the varicella zoster virus (VZV) antibody-specific index and autoantibody positivity in patients with all diagnoses (F00-F79) (p < 0.005). Furthermore, the rubella antibody-specific index proved to be significantly associated with neural autoantibody positivity (p < 0.001) across all patients (F00-F79), and in those with affective disorders (p < 0.01). Our results show that VZV and rubella antiviral antibodies are associated with a higher propensity to develop anti-neural autoantibodies, suggesting that the known association between viral infection and later developing psychiatric disorders may be partly attributable to the development of anti-neural autoimmunity.