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Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia.

ABSTRACT: Cognitive deficits are a central feature of schizophrenia whose etiology is not fully understood. Epstein Barr Virus (EBV) is a potentially neurotropic infectious agent that can generate persistent infections with immunomodulatory effects. Previous studies have found an association between EBV antibodies and cognitive functioning in different populations, but there has been limited investigation in schizophrenia. In this study, 84 individuals with schizophrenia were administered a comprehensive neuropsychological battery, the MATRICS Consensus Cognitive Battery (MCCB). Participants also provided a blood sample, from which antibodies to the EBV whole virion and specific proteins were measured. Multivariate models were constructed to determine the association between these antibodies and cognitive performance on the MCCB overall and domain scores. Using these models, we found a significant association between the MCCB overall percent composite score and level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. A significant association was also found for the MCCB social cognition domain with the level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. In all cases, a higher level of antibodies was associated with a lower level cognitive performance. These findings suggest that exposure to EBV may contribute to cognitive deficits in schizophrenia, a finding which may have implications for new methods of prevention and treatment.

SUBMITTER: Dickerson F

PROVIDER: S-EPMC8023564 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia.

Dickerson Faith F Katsafanas Emily E Origoni Andrea A Squire Amalia A Khushalani Sunil S Newman Theresa T Rowe Kelly K Stallings Cassie C Savage Christina L G CLG Sweeney Kevin K Nguyen Tanya T TT Breier Alan A Goff Donald D Ford Glen G Jones-Brando Lorraine L Yolken Robert R

Schizophrenia research 20210112

Cognitive deficits are a central feature of schizophrenia whose etiology is not fully understood. Epstein Barr Virus (EBV) is a potentially neurotropic infectious agent that can generate persistent infections with immunomodulatory effects. Previous studies have found an association between EBV antibodies and cognitive functioning in different populations, but there has been limited investigation in schizophrenia. In this study, 84 individuals with schizophrenia were administered a comprehensive ...[more]

PMID: 33450604

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Project description:The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.

Project description:BackgroundThe prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection, particularly in cases of primary intestinal lymphoproliferative diseases and inflammatory bowel disease (IBD).MethodsReceiver operating characteristic (ROC) curves were examined to determine suitable thresholds for plasma EBV DNA load in diagnosing intestinal EBV infection and predicting its prognosis.Results108 patients were retrospectively assigned to the test group, while 56 patients were included in the validation group. Plasma EBV DNA loads were significantly higher in the intestinal EBV infection group compared to the non-intestinal EBV infection group (Median: 2.02 × 102 copies/mL, interquartile range [IQR]: 5.49 × 101-6.34×103 copies/mL versus 4.2×101 copies/mL, IQR: 1.07 ×101-6.08×101 copies/mL; P < 0.0001). Plasma EBV DNA levels at 9.21×101 and 6.77×101 copies/mL proved beneficial for the identification and prognostication in intestinal EBV infection, respectively. Values of 0.82 and 0.71 were yielded by the area under the ROC curve (AUC) in the test cohort, corresponding to sensitivities of 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) and 87.5% (95%CI: 69%-95.66%), specificities of 83.33% (95%CI: 64.15%-93.32%) and 68.09% (95%CI: 53.83%-79.6%), positive predictive values (PPV) of 87.1% (95%CI: 71.15%-94.87%) and 58.33% (95%CI: 42.2%-72.86%), and positive likelihood ratios (LR+) of 5.06 and 2.74 in the validation cohort, respectively. Furthermore, a plasma EBV DNA load of 5.4×102 copies/mL helped differentiate IBD with intestinal EBV infection from primary intestinal EBV-positive lymphoproliferative disorders (PIEBV+LPDs), achieving an AUC of 0.85 within the test cohort, as well as 85% sensitivity (95%CI: 63.96%-94.76%), 91.67% specificity (95%CI: 64.61%-99.57%), 94.44% PPV (95%CI: 74.24%-99.72%), and an LR+ of 10.2 in the validation cohort.ConclusionsPlasma EBV DNA load demonstrates notable potential in distinguishing between different patient cohorts with intestinal EBV infection, although its sensitivity requires further optimization for clinical application.

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Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia.

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Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia.

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