Correlations between the Serum Antibody Levels to Herpes Family Viruses and Multi-parametric Immunity Characteristics with Clinical Symptoms in Episodic Remittent form of Paranoid Schizophrenia

Background: Recent etiological studies for schizophrenia have been focused on the herpes family viruses. The majority of these studies were aimed at detection of increased specific antibodies level. An important aspect of systemic immunological changes associated with infection by these viruses and clinical symptoms of schizophrenia has not been investigated.

The Goal of Investigation Was: to study the relationships of acute episodes of remittent paranoid schizophrenia and herpes virus infection (herpes simplex virus type 1 - HSV-1, herpes simplex virus type 2 - HSV-2, cytomegalovirus -CMV and Epstein-Barr virus -EBV) including the analysis of the correlations of clinical symptoms with serum antibody levels and multiparametric immunity characteristics.

Materials and Methods: 32 patients with paranoid schizophrenia (episodic remittent form) (F 20.03 by ICD-10) in acute psychotic state were examined. The controls included 15 healthy subjects comparable by the age and sex without mental diseases and visible symptoms of somatic pathology. Using immunological methods we determined the leukocyte content, the lymphocyte subpopulations and the leukocyte phagocytosis in «PHAGOTEST» ("EXBIO Praha", Czech Republic) with fluorescein (FITC)-labeled opsonized bacteria and calculated the phagocytic index (PhI), the circulating immune complexes (CIC) level by spectrophotometry. Total serum immunoglobulins (IgG and IgM as well as IgA) were determined by immunoturbidimetry. The antibodies against herpes viruses (both IgG and IgM) were determined using the ELISA test. Clinical psychiatric examinations, Brief Psychiatric Rating Scale (BPRS) were used for the clinical symptoms assessment. Statistic analysis included U Test (Mann-Whitney). Spearman’s rank correlation coefficient was also used.

Results: The maximal number of patients demonstrated the positive reaction for IgG to EBV (96%), HSV-1 (81%) and CMV (31%). The levels of IgM to all studied herpes viruses differed from 0.Only Ig M titers to all studied viruses significantly exceeded corresponding titers in patients in comparison with studied controls. The pattern of changes of immune parameters in controls differed from that in patients. The level of Ig M to HSV-2 was correlated with the unfolded reaction involving the humoral, cellular and phagocytic immunity and occurrence of clinical symptoms as "somatic concerns" (provisionally designated "hypochondriac" complex). Correlation of the content of Ig M to HSV-2 with immune reaction in the form of antibody-dependent cell-mediated cytotoxicity was associated with deployed anxiety-depressive syndrome ("affective" complex). Correlation of Ig M to HSV-2 with a comprehensive reaction cell immunity, collectively with acute immune response to EBV revealed conjugacy with the formation of a psychotic state. R varied from 0,37 to 0,86 (p<0,05). Acute infectious process unfolds in the network of a mixed herpetic infection, associated of HSV-1and CMV. The last one is outstanding due to significantly higher level of IgM in patients compared with controls for both viruses and high frequency of seropositive cases for HSV-1.

Discussion: The results have demonstrated pathogenesis lines virus - immune response – psychopathology. They suppose an acute infectious process caused by HSV- 2, with the support of EBV as an important pathogenetic stage of development of psychotic episodes of remittent schizophrenia.