TY - JOUR
T1 - Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia
T2 - Results from the VISTA study
AU - Breier, Alan
AU - Buchanan, Robert W.
AU - D'Souza, Deepak
AU - Nuechterlein, Keith
AU - Marder, Stephen
AU - Dunn, Walter
AU - Preskorn, Sheldon
AU - Macaluso, Matthew
AU - Wurfel, Brent
AU - Maguire, Gerald
AU - Kakar, Rishi
AU - Highum, Diane
AU - Hoffmeyer, Debra
AU - Coskinas, Evagelos
AU - Litman, Robert
AU - Vohs, Jenifer L.
AU - Radnovich, Alexander
AU - Francis, Michael M.
AU - Metzler, Emmalee
AU - Visco, Andrew
AU - Mehdiyoun, Nicole
AU - Yang, Ziyi
AU - Zhang, Ying
AU - Yolken, Robert H.
AU - Dickerson, Faith B.
N1 - Publisher Copyright:
© 2018
PY - 2019/4
Y1 - 2019/4
N2 - 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 N = 70; HSV-1 negative N = 96)from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 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 (p < 0.001)with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034)and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 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
AB - 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 N = 70; HSV-1 negative N = 96)from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 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 (p < 0.001)with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034)and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 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
KW - Cognition
KW - Herpes simplex virus-1
KW - Schizophrenia
KW - Valacyclovir
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UR - http://www.scopus.com/inward/citedby.url?scp=85056995897&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2018.11.002
DO - 10.1016/j.schres.2018.11.002
M3 - Article
C2 - 30478008
AN - SCOPUS:85056995897
SN - 0920-9964
VL - 206
SP - 291
EP - 299
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -