RESUMO
BACKGROUND: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population. METHODS: 170 subjects with schizophrenia (HSV-1 positive Nâ¯=â¯70; HSV-1 negative Nâ¯=â¯96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5â¯g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory. RESULTS: The HSV-1 positive group, as compared to the HSV-1 negative group, were older (pâ¯<â¯0.001) with fewer males (pâ¯=â¯0.003), and had a longer duration of illness (pâ¯=â¯0.008), more positive symptoms (pâ¯=â¯0.013), poorer quality of life (pâ¯=â¯0.034) and more impairment on the letter-number sequencing test, which is a measure of working memory (pâ¯=â¯0.045). Valacyclovir failed to significantly improve any of the cognitive indices, symptom or functioning measures. CONCLUSIONS: HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773.