title: Antiherpes virus-specific treatment and cognition in schizophrenia: a test-of-concept randomized double-blind placebo-controlled trial.
abstract: OBJECTIVE
  To test our hypothesis that valacyclovir, an antiherpes virus-specific medication, added to antipsychotics (APs) would improve cognitive performance and psychopathology among schizophrenia subjects exposed to neurotropic herpes simplex virus, type 1 (HSV1).
  
  
  METHODS
  Using a double-blind placebo-controlled design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily orally. At each visit, subjects were evaluated for severity of psychopathology and side effects using standardized scales and a study-specific semistructured checklist. A computerized neurocognitive battery validated on both schizophrenia and healthy subjects was administered at baseline and follow-up. Intent-to-treat analysis, using linear regression models that included all randomized subjects, were used to examine differential changes in cognition and psychopathology scores over 18 weeks between valacyclovir and placebo, accounting for placebo response.
  
  
  RESULTS
  Valacyclovir group improved in verbal memory, working memory, and visual object learning compared with placebo group. The effect sizes (Cohen's d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for the visual object learning. Psychotic symptom severity did not improve.
  
  
  CONCLUSIONS
  Supplemental valacyclovir may alleviate impairments in cognitive domains that are often observed in schizophrenia but not psychotic symptoms in those exposed to HSV1. If replicated, this approach could provide a novel strategy to treat cognitive impairments in a subgroup of schizophrenia subjects who can be reliably identified using a blood test.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. prasadkm@upmc.edu
authors.forename: Konasale M
authors.initials: KM
authors.lastname: Prasad
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Eack
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006561:Herpes Simplex / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D018259:Herpesvirus 1, Human; D006801:Humans; D007858:Learning; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir