Exploring the associations of herpes simplex virus infection and cognitive dysfunction in schizophrenia: Studies in India

BACKGROUND: Cognitive dysfunctions being core features of schizophrenia (SZ), cause disability, increase burden and are refractory to treatment. Viral infections are not risk factors for SZ, but growing evidence indicates infection with some neurotropic viruses, particularly Herpes simplex virus type 1 (HSV -1) as a risk factor for cognitive dysfunction. STUDIES IN INDIA: Three research studies in India are described. In the first, participants were evaluated for HSV-1 infection and cognitive functions (cases 198 and controls 100). In the second, patients and normal nonpsychotic control individuals were examined at baseline and followed up over 1–3 years (cases 138 and controls 88). In the third, a randomized, double-blind placebo-controlled antipsychotic adjunctive trial was conducted to examine the effect of anti-viral drug valacyclovir over 16 weeks on cognitive functioning (valacyclovir 30; placebo 32, treatment for 16 weeks). RESULTS OF INDIAN STUDIES: Cross-sectional study: HSV-1 infection was associated with modest dysfunction, especially on attention (accuracy) and spatial processing (speed). LONGITUDINAL STUDY: HSV-1 seropositive participants had lower scores at baseline on 6/16 measures, regardless of SZ diagnoses. At follow-up, there was a significant decline in HSV-1-positive participants for abstraction and mental flexibility and emotion discrimination. RANDOMIZED CONTROLLED TRIAL: Significantly, greater improvement in accuracy index of emotion discrimination in the valacyclovir-treated versus placebo sample was found. CONCLUSIONS: Indian studies are consistent with a causative role for HSV-1 in cognitive dysfunction regardless of SZ diagnosis; more rigorous studies of the causal hypothesis are needed, particularly larger randomized controlled trials.