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OBJECTIVE: Borrelia burgdorferi infection can affect the CNS and mimic psychiatric disorders. It is not known whether Borrelia burgdorferi contributes to overall psychiatric morbidity. The authors compared the prevalence of antibodies to Borrelia burgdorferi in groups of psychiatric patients and healthy subjects to find out whether there is an association between this infection and psychiatric morbidity. METHOD: Between 1995 and 1999 the authors screened for antibodies to Borrelia burgdorferi in 926 psychiatric patients consecutively admitted to Prague Psychiatric Center. They compared the results of this screening with findings from 884 consecutive healthy subjects who took part in an epidemiological survey of antibodies to Borrelia burgdorferi in the general population of the Czech Republic. Sera were tested by means of enzyme-linked immunosorbent assay. Circulating immune complexes were isolated by polyethylene glycol precipitation. To control for potential confounders, the two groups of patients and healthy subjects were matched according to gender and age. Results were obtained in a sample of 499 matched pairs. RESULTS: Among the matched pairs, 166 (33%) of the psychiatric patients and 94 (19%) of the healthy comparison subjects were seropositive in at least one of the four assays. CONCLUSIONS: These findings support the hypothesis that there is an association between Borrelia burgdorferi infection and psychiatric morbidity. In countries where this infection is endemic, a proportion of psychiatric inpatients may be suffering from neuropathogenic effects of Borrelia burgdorferi.