Emotion discrimination in humans: Its association with HSV-1 infection and its improvement with antiviral treatment

Triptish Bhatia, Joel Wood, Satish Iyengar, Sreelatha S. Narayanan, Ram Pratap Beniwal, Konasale M. Prasad, Kehui Chen, Robert H. Yolken, Faith Dickerson, Ruben C. Gur, Raquel E. Gur, Smita N. Deshpande, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia – even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable. Methods: In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N = 226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5 G twice daily for 16 weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N = 67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT). Results: PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p = 0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p = 0.03). RCT: EMOD improved in VAL-treated patients (p = 0.048, Cohen's d = 0.43). Conclusions: A proportion of age related decline in EMOD is attributable to HSV-1 infection.

Original languageEnglish (US)
Pages (from-to)161-167
Number of pages7
JournalSchizophrenia Research
StatePublished - Mar 2018


  • Cognition
  • Emotion
  • HSV-1
  • Herpes virus
  • Memory
  • Schizophrenia
  • Valacyclovir

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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