The neurobiology of mood states is complicated by exposure to everyday stressors (e.g., psychosocial, ubiquitous environmental infections like CMV), each fluctuating between latency and reactivation. CMV reactivation induces proinflammatory cytokines (e.g., TNF-alpha) associated with induction of neurotoxic metabolites and the presence of mood states in bipolar disorder (BD). Whether CMV reactivation is associated with bipolar diagnoses (trait) or specific mood states is unclear. We investigated 139 BD type I and 99 healthy controls to determine if concentrations of IgG antibodies to Herpesviridae (e.g., CMV, HSV-1, and HSV-2) were associated with BD-I diagnosis and specific mood states. We found higher CMV antibody concentration in BD-I than in healthy controls (T234 = 3.1, P uncorr = 0.002; P corr = 0.006) but no difference in HSV-1 (P > 0.10) or HSV-2 (P > 0.10). Compared to euthymic BD-I volunteers, CMV IgG was higher in BD-I volunteers with elevated moods (P < 0.03) but not different in depressed moods (P > 0.10). While relationships presented between BD-I diagnosis, mood states, and CMV antibodies are encouraging, they are limited by the study's cross sectional nature. Nevertheless, further testing is warranted to replicate findings and determine whether reactivation of CMV infection exacerbates elevated mood states in BD-I
Showing posts with label cytomegalovirus. Show all posts
Showing posts with label cytomegalovirus. Show all posts
Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort. - PubMed - NCBI
"Numerous cross-sectional studies have related exposure to neurotropic infectious agents with cognitive dysfunction in older adults, however, the temporal sequence is uncertain.
METHODS:
In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for 5 years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders.
RESULTS:
The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX, and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection.
CONCLUSIONS:
Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age-related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment."
'via Blog this'
METHODS:
In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for 5 years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders.
RESULTS:
The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX, and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection.
CONCLUSIONS:
Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age-related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment."
'via Blog this'
Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease. - PubMed - NCBI
Alzheimer's disease (AD) has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV) is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs) from AD patients and non-demented (ND) controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ) protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology.
Latent virus and life expectancy: Virus shortens telomeres - Medical News Today
The telomeres are repetitive DNA sequences at each end of our chromosomes. Studies show that in every cell division, the telomere is shortened. As a result, the telomere limits the cell to a fixed number of divisions and a limited life span. An essential part of human cells they affect how our cells age - as people with longer telomeres live longer lives. Surprisingly, people who are infected with a latent virus, that is, an asymptomatic virus, have shorter telomeres. This is an important observation and a great mystery. Is the virus causing the telomere shortening, and how? And if this is the case, what does it mean in terms of the relationship between the latent viruses and longevity?
Now, an article "The Latent Cytomegalovirus Decreases Telomere Length By Microcompetition" by Hanan Polansky and Adrian Javaherian, published in Open Medicine by De Gruyter Open, provides some answers to these questions. As it turns out, a certain gene, called telomere repeat binding factor 2 (Terf2), belongs to a complex of six telomere-associated proteins, termed shelterin. The protein produced by this gene protects the chromosome ends of the DNA from damage, and controls telomere maintenance by the telomerase enzyme. When does a cell produce the Terf2 protein? After receiving a signal that tells a transcription factor called GABP to bind the Terf2 gene. One can think of GABP as a finger that pushes the "ON" button on the Terf2 gene. Now consider a case where a latent virus called CMV infects the cell. As it turns out, the CMV virus also uses the GABP transcription factor to press the "ON" button on its own genes. When the CMV virus steals the GABP "fingers" from the Terf2 gene, there are no fingers left to press the "ON" button on the Terf2 gene, and the Terf2 gene fails to produce the Terf2 protein. What is the result of a shortage of Terf2 proteins? Short telomeres. In his book "Microcompetition with Foreign DNA and the Origin of Chronic Disease", Dr. Polansky used the term Microcompetition to describe this event.
Translational Psychiatry - Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis
Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975–1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1–4.0) or cytomegalovirus (1.7, 0.9–3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal–fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders.
Scientists prove link between viral infection (cytomegalovirus) and autoimmune disease
Published in the leading journal Immunity, the Australian
research found that chronic cytomegalovirus (CMV) infection could lead
to the development of Sjogren's (SHOW-grins) syndrome.
CMV - a member of the herpes family - is a common viral infection
that causes mild flu-like symptoms in healthy people but can lead to
more serious illness in those with compromised immune systems.
Between 50 and 80 per cent of people in developed countries are
infected with CMV. Although normally innocuous, given the right genetic
background, chronic viral infection with CMV can trigger autoimmunity.
"Sjogren's syndrome (SS) is the second most common autoimmune disease
in humans, affecting up to three per cent of the population or more
than four million people in the United States alone," Professor
Degli-Esposti said.
research found that chronic cytomegalovirus (CMV) infection could lead
to the development of Sjogren's (SHOW-grins) syndrome.
CMV - a member of the herpes family - is a common viral infection
that causes mild flu-like symptoms in healthy people but can lead to
more serious illness in those with compromised immune systems.
Between 50 and 80 per cent of people in developed countries are
infected with CMV. Although normally innocuous, given the right genetic
background, chronic viral infection with CMV can trigger autoimmunity.
"Sjogren's syndrome (SS) is the second most common autoimmune disease
in humans, affecting up to three per cent of the population or more
than four million people in the United States alone," Professor
Degli-Esposti said.
Cytomegalovirus seropositivity is negatively associated with multiple sclerosis.
BACKGROUND:
Epidemiological data suggest arole for common viruses in the pathogenesis of multiple sclerosis (MS),
and recent data showed a negative association of past cytomegalovirus
(CMV) infection on pediatric MS risk.
OBJECTIVE:
Our aim was to analyze the association of CMV infection with MS risk in an adultcase-control material. A meta-analysis was performed to validate our findings.
METHODS:
Epidemiological Investigation in MS (EIMS) is a case-control study with incident cases and population-based controls. Anti-CMV antibody titers were measured with ELISA, and HLA-Aand DRB1 genotyping was performed with SSP-PCR, in 658 MS cases, who all fulfilled the McDonald criteria for MS, and 786 controls.
RESULTS:
CMV seropositivity was associated with a decreased MS risk, OR = 0.73(0.58-0.92 95% CI), p = 0.005, adjusted for index age, gender, smoking,
sun exposure, EBNA1 IgG titer and HLA-A*02 and DRB1*15. When we removed
all cases and controls younger than 18 years at index, the protective
effect was still apparent.
CONCLUSIONS:
CMV is negatively associated with adult-onset MS pathology, consistent with results from astudy on pediatric MS cases. It remains to be shown whether this
negative association is due to a true protective effect of CMV infection
on MS risk.
Herpesviruses, Inflammatory Markers and Incident Depression in a Longitudinal Study of Detroit Residents - Psychoneuroendocrinology
Depression is predicted to become the leading cause of disability in the U.S by 2030 and moreover, socioeconomic inequalities in depression persist. Herpesviruses, which are more prevalent among socioeconomically disadvantaged populations, subject to stress-induced reactivation and are associated with increased levels of pro-inflammatory cytokines implicated in the etiology of depression, may serve as novel risk factors for depression onset.
Methods
Data are from individuals in the Detroit Neighborhood Health Study tested for herpes simplex virus-1 (HSV-1) and cytomegalovirus (CMV) seropositivity/Immunoglobulin G (IgG) antibody levels (N = 263) as well as interleukin-6 (IL-6) (N = 245) and C-reactive protein (CRP) (N = 236) levels and assessed for incident depression via the Patient Health Questionnaire-9. Linear and logistic regression models were used to examine associations between pathogen seropositivity/IgG antibody levels, pro-inflammatory markers and incident depression over approximately one-year of follow-up.Results
For every one unit increase in CMV IgG antibody level, the odds of incident depression increased by 26% and individuals with IgG antibody levels in the highest quartile had over three times greater odds of incident depression (odds ratio 3.87, 95% confidence interval 1.47, 10.19), compared to those in the lower three quartiles. Neither CMV or HSV-1 seropositivity nor HSV-1 IgG antibody level were associated with IL-6 or CRP levels at Wave 1, nor were IL-6 or CRP levels associated with incident depression at Wave 2.Conclusions
Further examination of the biological pathways linking CMV and depression are warranted.Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder.
has a limbic and temporal gray matter tropism. It is usually latent in
humans but has been associated with schizophrenia, bipolar disorder and
cognitive deficits in some populations. Hippocampal decreased volume and
dysfunction play a critical role in these cognitive deficits. We
hypothesized that CMV seropositivity and serointensity would be
associated with hippocampal volume and cognitive functioning in patients
with schizophrenia or bipolar disorder.
METHODS:
102 healthy controls, 118 patients with bipolar disorder and 69 patientswith schizophrenia performed the California Verbal Learning Test (CVLT)
and had blood samples drawn to assess CMV IgG levels. A subgroup of 52
healthy controls, 31 patients with bipolar disorder and 27 patients with
schizophrenia underwent T1 MRI for hippocampal volumetry. We analyzed
the association between CMV serointensity and seropositivity with
hippocampal volume. We also explored the correlation between CMV
serointensity and seropositivity and CVLT scores.
RESULTS:
In both patient groups but not in controls, higher CMV serointensity wassignificantly associated with smaller right hippocampal volume. Further,
in the group of patients with schizophrenia but not bipolar disorder,
CMV serointensity was negatively correlated with CVLT scores.
CONCLUSION:
CMV IgG titers are associated with decreased hippocampal volume and poorerepisodic verbal memory in patients with schizophrenia or bipolar
disorder. The mechanism of this association warrants further
exploration.
Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder.
OBJECTIVE:
Bipolar disorder (BD) has been associated withpersistent low-grade inflammation and premature cell senescence, as
shown by reduced telomere length (TL). The human cytomegalovirus (CMV)
has increasingly been implicated in accelerated immunosenescence in
aging studies. Here, we compared CMV serology and its relationships with
cell senescence markers, including TL and lymphocyte subsets, in
patients with type I BD and healthy controls.
METHODS:
Twenty-twoeuthymic female patients with BD type I and 17 age-matched healthy
controls were selected for the study. A sample of blood was collected
and mononuclear cells and DNA were isolated and TL measured. CMV
immunoglobulin M (IgM) and IgG titers were measured using
chemiluminescent assays. Lymphocyte subsets [T, natural killer (NK) and
NKT] were phenotyped by flow cytometry.
RESULTS:
Individualswith BD had shorter TLs but higher CMV IgG levels than controls (both p
< 0.01). CMV IgG level was inversely correlated with TL. None of the
subjects showed IgM reactivity for CMV, excluding acute viral
infection. CMV IgG level was associated with expansion of senescent
CD8+CD28- T cells and NK cells, which are involved in viral control.
CONCLUSIONS:
Thesedata support the hypothesis of accelerated aging in BD, as shown by
shortened telomeres, higher seropositivity for CMV, and expansion of
senescent T cells.
CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses.
A wide range of antiviral drugs is currently available; however,
drug-resistant viruses have begun to emerge and represent a potential
public health risk. Here, we explored the use of compounds that inhibit
or interfere with the action of essential host factors to prevent virus
replication. In particular, we focused on the cyclin-dependent kinase 9
(CDK9) inhibitor, FIT-039, which suppressed replication of a broad
spectrum of DNA viruses through inhibition of mRNA transcription.
Specifically, FIT-039 inhibited replication of herpes simplex virus 1
(HSV-1), HSV-2, human adenovirus, and human cytomegalovirus in cultured
cells, and topical application of FIT-039 ointment suppressed skin
legion formation in a murine HSV-1 infection model. FIT-039 did not
affect cell cycle progression or cellular proliferation in host cells.
Compared with the general CDK inhibitor flavopiridol, transcriptome
analyses of FIT-039-treated cells revealed that FIT-039 specifically
inhibited CDK9. Given at concentrations above the inhibitory
concentration, FIT-039 did not have a cytotoxic effect on mammalian
cells. Importantly, administration of FIT-039 ameliorated the severity
of skin lesion formation in mice infected with an acyclovir-resistant
HSV-1, without noticeable adverse effects. Together, these data indicate
that FIT-039 has potential as an antiviral agent for clinical
therapeutics.
drug-resistant viruses have begun to emerge and represent a potential
public health risk. Here, we explored the use of compounds that inhibit
or interfere with the action of essential host factors to prevent virus
replication. In particular, we focused on the cyclin-dependent kinase 9
(CDK9) inhibitor, FIT-039, which suppressed replication of a broad
spectrum of DNA viruses through inhibition of mRNA transcription.
Specifically, FIT-039 inhibited replication of herpes simplex virus 1
(HSV-1), HSV-2, human adenovirus, and human cytomegalovirus in cultured
cells, and topical application of FIT-039 ointment suppressed skin
legion formation in a murine HSV-1 infection model. FIT-039 did not
affect cell cycle progression or cellular proliferation in host cells.
Compared with the general CDK inhibitor flavopiridol, transcriptome
analyses of FIT-039-treated cells revealed that FIT-039 specifically
inhibited CDK9. Given at concentrations above the inhibitory
concentration, FIT-039 did not have a cytotoxic effect on mammalian
cells. Importantly, administration of FIT-039 ameliorated the severity
of skin lesion formation in mice infected with an acyclovir-resistant
HSV-1, without noticeable adverse effects. Together, these data indicate
that FIT-039 has potential as an antiviral agent for clinical
therapeutics.
A study on the association between infectious burden and Alzheimer's disease.
BACKGROUND AND PURPOSE:
Previous studies suggested that the overall burden of prior infections contributes to cardiovasculardiseases and stroke. In the present study, the association between
infectious burden (IB) and Alzheimer's disease (AD) was examined.
METHODS:
Antibody titers to common infectious pathogens including cytomegalovirus (CMV),herpes simplex virus type 1 (HSV-1), Borrelia burgdorferi, Chlamydophila
pneumoniae and Helicobacter pylori were measured by enzyme-linked
immunosorbent assay in 128 AD patients and 135 healthy controls. IB was
defined as a composite serological measure of exposure to these common
pathogens.
RESULTS:
Seropositivities toward zero-two, three and four-five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini-Mental State Examination scores were negatively correlated with IB in all cases. Serum beta-amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon-γ, tumor necrosis factor α, interleukin-1β and interleukin-6) in individuals exposed to four-five infectious pathogens were significantly higher than those exposed to zero-two or three pathogens.CONCLUSIONS:
IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
Quantitative Temporal Viromics: An Approach to Investigate Host-Pathogen Interaction: Cell
A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection could provide dynamic insights into virus-host interaction. We developed a proteomic technique called “quantitative temporal viromics” (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV orchestrates the expression of >8,000 cellular proteins, including 1,200 cell-surface proteins to manipulate signaling pathways and counterintrinsic, innate, and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined. QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model.
Persistent Viral Pathogens and Cognitive Impairment Across the Life Course in the Third National Health and Nutrition Examination Survey
Background. Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population.
Methods. We determined whether cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) seropositivity were associated with cognitive impairment among children (aged 6–16 years) and adults aged 20–59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
Results. Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (β, −0.69; 95% confidence interval [CI], −1.18 to −.21 and β, −0.82; 95% CI, −1.29 to −.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13–2.11, and OR, 1.41; 95% CI, 1.09–1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14–1.80). Among older
adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68–6.32).
adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68–6.32).
Conclusions. Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.
Persistent Viral Pathogens and Cognitive Impairment Across the Life Course in the Third National Health and Nutrition Examination Survey
Background. Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population.
Methods. We determined whether cytomegalovirus (CMV) and herpes simplex virus 1
(HSV-1) seropositivity were associated with cognitive impairment among children (aged 6–16 years) and adults aged 20–59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
(HSV-1) seropositivity were associated with cognitive impairment among children (aged 6–16 years) and adults aged 20–59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
Results. Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (β, −0.69; 95% confidence interval [CI], −1.18 to −.21 and β, −0.82; 95% CI,
−1.29 to −.36, respectively).
Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13–2.11, and OR, 1.41; 95% CI, 1.09–1.82,
respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14–1.80). Among older adults, HSV-1 seropositivity was associated with immediate
memory impairment (OR, 3.26; 95% CI, 1.68–6.32).
−1.29 to −.36, respectively).
Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13–2.11, and OR, 1.41; 95% CI, 1.09–1.82,
respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14–1.80). Among older adults, HSV-1 seropositivity was associated with immediate
memory impairment (OR, 3.26; 95% CI, 1.68–6.32).
Conclusions. Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.
Persistent Viral Pathogens and Cognitive Impairment across the Lifecourse in the Third National Health and Nutrition Examination Survey
Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general U.S. population.
Methods. We examined whether cytomegalovirus (CMV) and herpes simplex virus-1 (HSV-1) seropositivity were associated with cognitive impairment among children 6-16, adults 20-59 and adults 60 years of age and older using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
Results. Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (β=-0.69, 95% Confidence Interval (CI), -1.18, -0.21 and β=-0.82, 95% CI, -1.29, -0.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (Odds Ratio (OR)=1.54; 95% CI, 1.13, 2.11 and OR=1.41; 95% CI, 1.09, 1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR=1.43; 95% CI, 1.14, 1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR=3.26; 95% CI, 1.68, 6.32).
Conclusion. Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the lifecourse are warranted.
Methods. We examined whether cytomegalovirus (CMV) and herpes simplex virus-1 (HSV-1) seropositivity were associated with cognitive impairment among children 6-16, adults 20-59 and adults 60 years of age and older using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
Results. Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (β=-0.69, 95% Confidence Interval (CI), -1.18, -0.21 and β=-0.82, 95% CI, -1.29, -0.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (Odds Ratio (OR)=1.54; 95% CI, 1.13, 2.11 and OR=1.41; 95% CI, 1.09, 1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR=1.43; 95% CI, 1.14, 1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR=3.26; 95% CI, 1.68, 6.32).
Conclusion. Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the lifecourse are warranted.
Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection.
Populations of human cytomegalovirus (HCMV), a large DNA virus, are highly polymorphic in patient samples, which may allow for rapid evolution within human hosts. To understand HCMV evolution, longitudinally sampled genomic populations from the urine and plasma of 5 infants with symptomatic congenital HCMV infection were analyzed. Temporal and compartmental variability of viral populations were quantified using high throughput sequencing and population genetics approaches. HCMVpopulations were generally stable over time, with ∼88% of SNPs displaying similar frequencies. However, samples collected from plasma and urine of the same patient at the same time were highly differentiated with approximately 1700 consensus sequence SNPs (1.2% of the genome) identified between compartments. This inter-compartment differentiation was comparable to the differentiation observed in unrelated hosts. Models of demography (i.e., changes in population size and structure) and positive selection were evaluated to explain the observed patterns of variation. Evidence for strong bottlenecks (>90% reduction in viral population size) was consistent among all patients. From the timing of the bottlenecks, we conclude that fetal infection occurred between 13-18 weeks gestational age in patients analyzed, while colonization of the urine compartment followed roughly 2 months later. The timing of these bottlenecks is consistent with the clinical histories of congenital HCMV infections. We next inferred that positive selection plays a small but measurable role in viral evolution within a single compartment. However, positive selection appears to be a strong and pervasive driver of evolution associated with compartmentalization, affecting ≥34 of the 167 open reading frames (∼20%) of the genome. This work offers the most detailed map of HCMV in vivo evolution to date and provides evidence that viral populations can be stable or rapidly differentiate, depending on host environment. The application of population genetic methods to these data provides clinically useful information, such as the timing of infection and compartment colonization.
Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder.
Cytomegalovirus (CMV) is a member of the herpesviridae family that has a limbic and temporal gray matter tropism. It is usually latent in humans but has been associated with schizophrenia, bipolar disorder and cognitive deficits in some populations. Hippocampal decreased volume and dysfunction play a critical role in these cognitive deficits. We hypothesized that CMV seropositivity and serointensity would be associated with hippocampal volume and cognitive functioning in patients with schizophrenia or bipolar disorder.
METHODS:
102 healthy controls, 118 patients with bipolar disorder and 69 patients with schizophrenia performed the California Verbal Learning Test (CVLT) and had blood samples drawn to assess CMV IgG levels. A subgroup of 52 healthy controls, 31 patients with bipolar disorder and 27 patients with schizophrenia underwent T1 MRI for hippocampal volumetry. We analyzed the association between CMV serointensity and seropositivity with hippocampal volume. We also explored the correlation between CMV serointensitiy and seropositivity and CVLT scores.
RESULTS:
In both patients groups but not in controls, higher CMV serointensity was significantly associated with smaller right hippocampal volume. Further, in the group of patients with schizophrenia but not bipolar disorder, CMV serointensity was negatively correlated with CVLT scores.
CONCLUSION:
CMV IgG titers are associated with decreased hippocampal volume and poorer episodic verbal memory in patients with schizophrenia or bipolar disorder. The mechanism of this association warrants further exploration.
Cytomegalovirus antibody elevation: A potential bio-marker of impulsivity in bipolar disorder
Approximately 1/3 of Bipolar Disorder (BD) patients attempt suicide, often in the context of exacerbated impulsivity. In humans and animal models, a buildup of neurotoxic metabolites and contributes to orbital frontal white matter abnormalities. Hypofrontality is associated with impulsivity. However, what factors contribute to mechanisms underlying these cerebral alterations in humans in general and BD in particular remain unclear. Ubiquitous environmental human infections (Cytomegalovirus;CMV), fluctuate between latency and reactivation, potentially triggered by exposure to psychosocial stressors. While CMV reactivation has been shown to induce pro-inflammatory cytokines (e.g. TNF-α) which are themselves associated with depression, suicidality, and neurotoxic metabolite induction, investigations of CMV and its contribution to impulsivity in BD are lacking. We investigated 150 BD type I and 109 healthy control volunteers to determine if CMV IgG antibody concentrations were associated with measures of impulsivity and suicidality in BD-I. Using standard viral assay techniques, we quantified plasma CMV IgG antibodies. CMV antibody concentration was higher in BD-I than in healthy control volunteers (T254 = 2.9, p = 0.004), significantly correlating with measures of neurotic coping style (NEO-PI N5 impulsivity) (p < 0.05) which further correlated to other clinical measures of impulsivity (BIS-11) (r = 0.44, p = 0.002). This is the first study to identify a diagnostic relationship between BD-I and CMV antibodies. The data presented supports the hypothesis that CMV infection and subsequent immune activation may contribute to exacerbation of impulsive behavior in BD-I.
Subscribe to:
Posts (Atom)