Alan Breier1, Robert W Buchanan2, Deepak D'Souza3, Keith Nuechterlein4, Stephen Marder4, Walter Dunn4, Sheldon Preskorn5, Matthew Macaluso5, Brent Wurfel6, Gerald Maguire7, Rishi Kakar8, Diane Highum9, Debra Hoffmeyer9, Evagelos Coskinas10, Robert Litman11, Jenifer L Vohs12, Alexander Radnovich12, Michael M Francis12, Emmalee Metzler12, Andrew Visco12, Nicole Mehdiyoun12, Ziyi Yang12, Ying Zhang12, Robert H Yolken13, Faith B Dickerson14. 1. Indiana University School of Medicine, Indianapolis, IN, United States of America. Electronic address: abreier@iupui.edu. 2. Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD, United States of America. 3. Yale University School of Medicine, New Haven, CT, United States of America. 4. Semel Institute, UCLA, Los Angeles, CA, United States of America. 5. Kansas University School of Medicine, Wichita, KS, United States of America. 6. Laureate Institute for Brain Research, KS, United States of America. 7. University of California, Riverside, CA, United States of America. 8. Segal Institute for Clinical Research, United States of America. 9. CITrials, Bellflower, CA, United States of America. 10. CITrials, Santa Ana, CA, United States of America. 11. CBH Health, Rockville, MD, United States of America. 12. Indiana University School of Medicine, Indianapolis, IN, United States of America. 13. Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. 14. Sheppard Pratt Health System, Baltimore, MD, United States of America.
Abstract
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-1positive N = 70; HSV-1 negativeN = 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 Identifier: NCT02008773.
RCT Entities:
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-1sero-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.
Authors: Faith Dickerson; Emily Katsafanas; Andrea Origoni; Amalia Squire; Sunil Khushalani; Theresa Newman; Kelly Rowe; Cassie Stallings; Christina L G Savage; Kevin Sweeney; Tanya T Nguyen; Alan Breier; Donald Goff; Glen Ford; Lorraine Jones-Brando; Robert Yolken Journal: Schizophr Res Date: 2021-01-12 Impact factor: 4.939