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BACKGROUND: Recent etiological studies for schizophrenia and bipolar disorder have focused on the protozoan Toxoplasma gondii and Herpesvirdae family viruses. OBJECTIVE: To determine the magnitude of T. gondii, cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection in individuals with schizophrenia, bipolar disorder and healthy controls by using serologic diagnostic methods. MATERIAL AND METHODS: Serologic diagnostic method was used to determine the prevalence and level of antibodies to T gondii, CMV HSV-1 and HSV-2 in individuals with schizophrenia, bipolar disorder, and unaffected controls recruited from Butajira, Ethiopia. The study was conducted from March to May 2009. A total of 495 serum samples were analysed for the presence and level of immunoglobulin G (IgG) to T. gondii, CMV HSV-1, and HSV-2. RESULTS: The seroprevalence of T gondii infection was higher in individuals with schizophrenia [adjusted odds ratio = 4.7; 95% CI (1.5, 15.1)] and bipolar disorder [adjusted odds ratio = 3.0; 95% CI (1.1, 8.6)] than in unaffected controls. The level of IgG to CMV was also significantly higher in individuals with schizophrenia and bipoar disorder than in unaffected controls. Younger individuals with schizophrenia (< 25 years old) also had a significantly higher level of IgG to CMV than matched unaffected controls. CONCLUSION: This study provides additional evidence that infection with 7T gondii and CMV may be associated with some cases of schizophrenia and bipolar disorder. Additional studies should focus on antibodies to these agents in the sera and CSF of individuals with recent-onset psychosis.