Exposure to Herpes Simplex Virus Type 1 and Cognitive Impairments in Individuals With Schizophrenia
1Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA. Schizophrenia Bulletin
(Impact Factor: 8.45).
04/2012; 38(6). DOI: 10.1093/schbul/sbs046
Latent infection with neurotropic herpes viruses, such as herpes simplex virus, type 1 (HSV1), has been generally considered benign in most immunocompetent individuals except for rare cases of encephalitis. However, several recent studies have shown impaired cognitive functions among individuals with schizophrenia exposed to HSV1 compared with schizophrenia patients not exposed to HSV1. Such impairments are robust and are prominently observed in working memory, verbal memory, and executive functions. Brain regions that play a key role in the regulation of these domains have shown smaller volumes, along with correlation between these morphometric changes and cognitive impairments in schizophrenia. One study noted temporal decline in executive function and gray matter loss among HSV1-exposed first-episode antipsychotic-naïve schizophrenia patients. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes-specific medication among HSV1 seropositive schizophrenia patients. Cross-sectional studies have also identified an association between HSV1 exposure and lesser degrees of cognitive impairment among healthy control individuals and patients with bipolar disorder. These studies fulfill several Bradford-Hill criteria, suggesting etiological links between HSV1 exposure and cognitive impairment. Exposure to other human herpes viruses such as cytomegalovirus and herpes simplex virus type 2 (HSV2) may also be associated with cognitive impairment, but the data are less consistent. These studies are reviewed critically and further lines of enquiry recommended. The results are important from a public health perspective, as HSV1 exposure is highly prevalent in many populations.
Available from: Robert Cloninger
- "gondii) and herpes viruses (cytomegalovirus, HSV1), have been linked to multiple psychiatric disorders including schizophrenia and bipolar disorder. (Pearce et al., 2012; Prasad et al., 2012; Tedla et al., 2011; Torrey et al., 2012). Latent toxoplasmosis, the asymptomatic persistence of cysts in host tissues, including the brain, is prevalent in 25e30% of the global population (Pappas et al., 2009) with a relatively lower prevalence (10e15%) reported in the US (Dubey and Jones, 2008). "
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Latent chronic infection with Toxoplasma gondii (T. gondii), a common neurotropic pathogen, has been previously linked with suicidal self-directed violence (SSDV). We sought to determine if latent infection with T. gondii is associated with trait aggression and impulsivity, intermediate phenotypes for suicidal behavior, in psychiatrically healthy adults.
Traits of aggression and impulsivity were analyzed in relationship to IgG antibody seropositivity for T. gondii and two other latent neurotropic infections, herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV). One thousand community-residing adults residing in the Munich metropolitan area with no Axis I or II conditions by SCID for DSM-IV (510 men, 490 women, mean age 53.6 ± 15.8, range 20-74). Plasma samples were tested for IgG antibodies to T. gondii, HSV-1 and CMV by ELISA. Self-reported ratings of trait aggression scores (Questionnaire for Measuring Factors of Aggression [FAF]) and trait impulsivity (Sensation-Seeking Scale-V [SSS-V]) were analyzed using linear multivariate methods.
T. gondii IgG seropositivity was significantly associated with higher trait reactive aggression scores among women (p < .01), but not among men. T. gondii-positivity was also associated with higher impulsive sensation-seeking (SSS-V Disinhibition) among younger men (p < .01) aged 20-59 years old (median age = 60). All associations with HSV-1 and CMV were not significant.
Aggression and impulsivity, personality traits considered as endophenotypes for SSDV, are associated with latent T. gondii infection in a gender and age-specific manner, and could be further investigated as prognostic and treatment targets in T. gondii-positive individuals at risk for SSDV.
Journal of Psychiatric Research 09/2014; 60. DOI:10.1016/j.jpsychires.2014.09.019 · 3.96 Impact Factor
Available from: PubMed Central
- "Interestingly, VCV has been found to alleviate cognitive impairment in schizophrenia patients. A test-of-concept double-blind placebo-controlled trial by Prasad et al. (2012), assessed the effects of VCV on cognitive performance and psychopathology. Of 24 HSV1-seropositive patients aged 18–50 years, 12 were given 2 × 1.5 g VCV twice daily and 12 given placebo for 18 weeks, in addition to antipsychotics. "
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ABSTRACT: Abstract HSV1, when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in AD. It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervous system) under certain conditions, for example stress, immunosuppression, and peripheral infection, causing cumulative damage and eventually development of AD. Diverse approaches have provided data that explicitly support, directly or indirectly, these concepts. Several have confirmed HSV1 DNA presence in human brains, and the HSV1-APOE-ε4 association in AD. Further, studies on HSV1-infected APOE-transgenic mice have shown that APOE-e4 animals display a greater potential for viral damage. Reactivated HSV1 can cause direct and inflammatory damage, probably involving increased formation of beta amyloid (Aβ) and of AD-like tau (P-tau) - changes found to occur in HSV1-infected cell cultures. Implicating HSV1 further in AD is the discovery that HSV1 DNA is specifically localised in amyloid plaques in AD. Other relevant, harmful effects of infection include the following: dynamic interactions between HSV1 and amyloid precursor protein (APP), which would affect both viral and APP transport; induction of toll-like receptors in HSV1-infected astrocyte cultures, which has been linked to the likely effects of reactivation of the virus in brain. Several epidemiological studies have shown, using serological data, an association between systemic infections and cognitive decline, with HSV1 particularly implicated. Genetic studies too have linked various pathways in AD with those occurring on HSV1 infection. In relation to the potential usage of antivirals to treat AD patients, acyclovir (ACV) is effective in reducing HSV1-induced AD-like changes in cell cultures, and valacyclovir, the bioactive form of ACV, might be most effective if combined with an antiviral that acts by a different mechanism, such as
Frontiers in Aging Neuroscience 08/2014; 6:202. DOI:10.3389/fnagi.2014.00202 · 4.00 Impact Factor
Available from: Hans Klein
- "Although the factors that cause cognitive impairment are largely unknown, it is suggested that the presence of antibodies to herpes simplex virus 1 (HSV1) may play a role. A recent review summarized several studies that found that HSV1 antibodies were associated with impaired immediate memory and executive functioning in patients with schizophrenia . This association was also found in patients with bipolar disorder , . "
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Infections with different herpes viruses have been associated with cognitive functioning in psychiatric patients and healthy adults. The aim of this study was to find out whether antibodies to different herpes viruses are prospectively associated with cognitive functioning in a general adolescent population.
This study was performed in TRAILS, a large prospective general population cohort (N = 1084, 54% female, mean age 16.2 years (SD 0.6)). At age 16, immunoglobulin G antibodies against HSV1, HSV2, CMV and EBV were measured next to high sensitive C-Reactive Protein (hsCRP). Two years later, immediate memory and executive functioning were assessed using the 15 words task and the self ordered pointing task. Multiple linear regression analysis with bootstrapping was performed to study the association between viral infections and cognitive function, adjusting for gender, socioeconomic status, ethnicity, and cannabis use.
Presence of HSV1 antibodies was associated with memory function ((B = −0.272, 95% CI = −0.556 to −0.016, p = 0.047)), while the association with executive functioning did not reach statistical significance (B = 0.560, 95% CI is −0.053 to 1.184, p = 0.075). The level of HSV1 antibodies was associated with both memory function (B = −0.160, 95% CI = −0.280 to −0.039, p = 0.014) and executive functioning (B = 0.296, 95% CI = 0.011 to 0.578, p = 0.046). Other herpes viruses and hsCRP were not associated with cognitive functioning.
Both presence and level of HSV1 antibodies are prospectively associated with reduced cognitive performance in a large cohort of adolescents.
PLoS ONE 07/2014; 9(7):e101549. DOI:10.1371/journal.pone.0101549 · 3.23 Impact Factor
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