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

Dickerson, Faith; Katsafanas, Emily; Origoni, Andrea; Squire, Amalia; Khushalani, Sunil; Newman, Theresa; Rowe, Kelly; Stallings, Cassie; Savage, Christina; Sweeney, Kevin; Nguyen, Tanya; Breier, Alan; Goff, Donald C.; Ford, Glen; Jones‐Brando, Lorraine; Yolken, Robert H.

doi:10.1016/j.schres.2020.12.018

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…Indeed, by including a population of community-dwelling individuals and using measures of executive functioning, the present study suggests that EBV antibody titers may be associated with cognitive performance before the onset of clinically relevant cognitive decline. Similar findings have been demonstrated among those with schizophrenia (34), but not among those diagnosed with multiple sclerosis (35). Interestingly, herpes simplex 1, but not EBV, antibody levels were associated with executive functioning among a sample of adolescents (36).…”

Section: Discussionsupporting

confidence: 79%

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults

Murdock

Stowe

Engeland³

2022

Psychosom Med

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ObjectiveWithin the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies.MethodsWe investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1β, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study.ResultsFindings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition (B = −2.36, standard error = 1.06, p = .028) and cognitive flexibility (B = −2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses.ConclusionsThese results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

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Section: Discussionsupporting

confidence: 79%

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults

Murdock

Stowe

Engeland³

2022

Psychosom Med

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“…In several previous studies, no differences in antibody levels of SSD patients with control populations have been observed [ 4 , 59 ], whereas other studies reported elevated antibodies against the EBV VCA protein and whole virion with no differences in EBV EBNA-1 antibodies [ 11 ]. Elevated levels of EBV antibodies are associated, on the one hand, in combination with genetic susceptibility to schizophrenia with a greater risk for schizophrenia diagnosis [ 11 ], and on the other hand, with a lower level of cognitive performance [ 12 ]. The latter is of great interest, since in this study a correlation between the EBV-specific AI and the AMDP score for disturbances of orientation was observed.…”

Section: Discussionmentioning

confidence: 99%

“…There is little information available on EBV infections and the chronicity of SSDs. Although it is well-known that EBV causes latent infections in a wide variety of body regions, including the brain, with the potential to reactivate [ 12 ]. Such latent EBV infections and reactivations in the CNS have been associated with encephalitis in stem cell recipients [ 30 ] and inflammatory immune reactions in active multiple sclerosis lesions [ 6 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders

Runge

Balla

Fiebich

et al. 2022

Fluids Barriers CNS

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Introduction Infectious and immunological theories of schizophrenia have been discussed for over a century. Contradictory results for infectious agents in association with schizophrenia spectrum disorders (SSDs) were reported. The rationale of this study was to investigate intrathecal antibody synthesis of the most frequently discussed neurotropic pathogens using a pathogen-specific antibody index (AI) in patients with SSD in comparison to controls. Methods In 100 patients with SSD and 39 mentally healthy controls with idiopathic intracranial hypertension (IIH), antibodies against the herpesviruses EBV, CMV, and HSV 1/2 as well as the protozoan Toxoplasma gondii, were measured in paired cerebrospinal fluid (CSF) and serum samples with ELISA-kits. From these antibody concentrations the pathogen-specific AIs were determined with the assumption of intrathecal antibody synthesis at values > 1.5. Results No significant difference was detected in the number of SSD patients with elevated pathogen-specific AI compared to the control group. In a subgroup analysis, a significantly higher EBV AI was observed in the group of patients with chronic SSD compared to patients with first-time SSD diagnosis (p = 0.003). In addition, two identified outlier EBV patients showed evidence for polyspecific immune reactions (with more than one increased AI). Conclusions Evidence for the role of intrathecal EBV antibody synthesis was found in patients with chronic SSD compared to those first diagnosed. Apart from a possible infectious factor in SSD pathophysiology, the evidence for polyspecific immune response in outlier patients may also suggest the involvement of further immunological processes in a small subgroup of SSD patients.

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“…People with schizophrenia had elevated levels of antibodies to EBV viruses compared to the control population [84]. The same research group in a recent study shown that there is a significant association between decreased cognitive performance in patients with schizophrenia as measured by the MATRICS Consensus Cognitive Battery (MCCB) and the levels of antibodies to EBV (anti-EBNA-1 and anti-VCA) [85]. Khandaker et al [86] shown a connection between EBV infection in childhood and an increased subsequent risk of psychotic experiences in adolescence.…”

Section: Ebvmentioning

confidence: 99%

Association between Prenatal Viral Infections and the Occurrence of Schizophrenia in Adulthood

Kotsiri

Spyrantis

Panotopoulos³

et al. 2022

JAMMR

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Schizophrenia is a severe mental disorder that affects approximately 1% of the population worldwide. Genetics and environmental factors appear to contribute to the pathogenesis of schizophrenia. Epidemiological studies have focused on the relationship between viral infection during pregnancy and an increased risk of developing schizophrenia in offspring. The aim of our review is to summarize whether viral infections during pregnancy can lead to psychiatric disorders and especially to schizophrenia in adulthood. For that purpose we undertaken a thorough search in Pubmed using as keywords viral infections, schizophrenia, perinatal infections and virus. Epidemiological studies have focused on the relationship between perinatal viral infections and an increased risk of developing schizophrenia in offspring. Influenza virus, various members of the Herpesviridae family, retroviruses, borna virus are discussed as examples of viral infections associated with schizophrenia. These viral infections appear to interfere with the normal maturation of the brain and may lead to the subsequent onset of schizophrenia. Another epidemiological aspect of schizophrenia is the fact that it presents a seasonal prevalence with peaks in offsprings which wer born during winter and spring. It is also possible for an infection occurring in infancy to reactivate later, as is known to happen with herpes viruses. Overall,various studies showed that prenatal maternal infections appear to increase the risk of developing schizophrenia in the offspring, and this is due to the body's immune response to the infection, and not in exposure to specific viral or bacterial pathogens.

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

Cited by 16 publications

References 28 publications

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults

Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders

Association between Prenatal Viral Infections and the Occurrence of Schizophrenia in Adulthood

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