Cognitive deficits are characteristic of schizophrenia but their etiology is not understood. Previous studies show an association between viral exposures and cognitive impairment. This meta-analysis was undertaken to determine the relationship of herpes simplex virus type 1 (HSV-1) exposure and cognitive functioning in schizophrenia. A systematic search was performed for studies comparing the cognitive functioning of HSV-1 seropositive vs. seronegative persons with schizophrenia. The primary outcome was the standardized mean difference (SMD) in composite cognitive score using Hedges’ g. Secondary outcomes were SMDs in 9cognitive domains. Study heterogeneity was estimated using the I index and formal tests of heterogeneity using Cochran’s Q. In a sample of 3516 individuals from 9 studies the SMD was negative for the composite score and all 9 domains indicating a significant deficit for seropositive individuals in 8 domains. The SMDs ranged from -0.11 (Working Memory) to -0.36 (Visual Spatial). Cochran’s Q test indicated heterogeneity for one domain. The I index of heterogeneity was in the low -moderate range for all but one domain. Exposure to HSV-1 is associated with decreased cognitive functioning in schizophrenia. An increased understanding of HSV-1 exposure might lead to improved methods for the prevention and treatment of cognitive deficits in schizophrenia.
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