Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 24
Filter
1.
BMC Psychiatry ; 16(1): 369, 2016 11 03.
Article in English | MEDLINE | ID: mdl-27809822

ABSTRACT

BACKGROUND: The hypothesis that microbial infections may be linked to mental disorders has long been addressed for Borna disease virus (BDV), but clinical and epidemiological evidence remained inconsistent due to non-conformities in detection methods. BDV circulating immune complexes (CIC) were shown to exceed the prevalence of serum antibodies alone and to comparably screen for infection in Europe (DE, CZ, IT), the Middle East (IR) and Asia (CN), still seeking general acceptance. METHODS: We used CIC and antigen (Ag) tests to investigate BDV infection in Lithuania through a case-control study design comparing in-patients suffering of primary psychosis with blood donors. One hundred and six acutely psychotic in-patients with no physical illness, consecutively admitted to the regional mental hospital, and 98 blood donors from the Blood Donation Centre, Lithuania, were enrolled in the study. The severity of psychosis was assessed twice, prior and after acute antipsychotic therapy, by the Brief Psychiatric Rating Scale (BPRS). BDV-CIC and Ag markers were tested once after therapy was terminated. RESULTS: What we found was a significantly higher prevalence of CIC, indicating a chronic BDV infection, in patients with treated primary psychosis than in blood donor controls (39.6 % vs. 22.4 %, respectively). Free BDV Ag, indicating currently active infection, did not show significant differences among study groups. Higher severity of psychosis prior to treatment was inversely correlated to the presence of BDV Ag (42.6 vs. 34.1 BPRS, respectively; p = 0.022). CONCLUSIONS: The study concluded significantly higher BDV infection rates in psychotic than in healthy Lithuanians, thus supporting similar global trends for other mental disorders. The study raised awareness to consider the integration of BDV infection surveillance in psychiatry research in the future.


Subject(s)
Borna Disease/epidemiology , Borna Disease/psychology , Borna disease virus , Psychotic Disorders/virology , Animals , Borna Disease/virology , Brief Psychiatric Rating Scale , Case-Control Studies , Female , Humans , Lithuania/epidemiology , Male , Prevalence , Psychotic Disorders/blood
2.
Fortschr Neurol Psychiatr ; 81(5): 250-9, 2013 May.
Article in German | MEDLINE | ID: mdl-23629631

ABSTRACT

The mild encephalitis (ME) hypothesis describes a subgroup of severe psychiatric disorders, with a focus on a subgroup of schizophrenias, in which low-level neuroinflammation (LLNI) represents the core in pathogenesis. LLNI is increasingly recognised in experimental neuroimmunology and is in principle able to explain various types of psychopathology. Epidemiology and course of schizophrenia are well compatible with the ME hypothesis, indirectly indicating that the ME subgroup may be rather large. With the ME model connected is a set of three contributing factors: genes, environment (especially infectious agents) and the immune system. The type of psychopathology observed in the individual case may heavily depend upon other conditions, e. g. pre-existing vulnerabilities. The first large-scale epidemiological study in psychiatry identified two factors during lifetime, severe infectious diseases and autoimmune diseases, as risk factors. This and clinical findings more and more support the ME hypothesis, e. g., activated monocytes or proteome changes in blood and slight CSF pathologies in more than 60 % of therapy-resistant schizophrenia, or activated microglia and dysconnectivity in neuroimaging.


Subject(s)
Encephalitis/pathology , Schizophrenia/pathology , Autoimmune Diseases/pathology , Autoimmune Diseases/psychology , Borna Disease/pathology , Borna Disease/psychology , Central Nervous System Infections/pathology , Central Nervous System Infections/psychology , Encephalitis/epidemiology , Encephalitis/psychology , Encephalitis/therapy , Humans , Schizophrenia/cerebrospinal fluid , Schizophrenia/epidemiology , Schizophrenia/therapy , Schizophrenic Psychology
3.
Mol Divers ; 8(3): 247-50, 2004.
Article in English | MEDLINE | ID: mdl-15384417

ABSTRACT

Borna Disease Virus (BDV) is suspected to infect humans and to be associated with psychiatric disorders. To this date, BDV-reactive antibodies provide the only reliable markers to diagnose human BDV infection. Their diagnostic value, however, was recently questioned by the observation that these antibodies recognize BDV antigen with only low avidity, a typical feature of cross-reacting antibodies. This raised the possibility that the human BDV-reactive antibodies were triggered by other pathogens than BDV. The recent establishment of a peptide array-based screening test allowed the further characterization of these antibodies. It revealed the presence of small amounts of BDV-reactive antibodies in crude human sera that specifically recognized various epitopes of three major BDV proteins. Most importantly, the purified epitope-specific antibodies were shown to bind to BDV antigen with high avidity when assayed by conventional immunofluorescence assay (IFA) or by Western blot. These results are compatible with the view that the presence of BDV-reactive antibodies in human sera reflects an infection with BDV, although the poor affinity maturation remains unexplained. Furthermore, it demonstrates that peptide array-based screening tests are a reliable system for identifying monospecific antibodies from human polyclonal sera with high specificity and sensitivity.


Subject(s)
Antibodies, Viral/blood , Borna Disease/diagnosis , Borna disease virus/genetics , Peptides/chemical synthesis , Protein Array Analysis , Psychotic Disorders/virology , Antibodies, Monoclonal , Antigens, Viral/blood , Borna Disease/psychology , Borna disease virus/isolation & purification , Humans , Peptides/chemistry , Psychotic Disorders/blood , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
4.
Proc Natl Acad Sci U S A ; 100(15): 8969-74, 2003 Jul 22.
Article in English | MEDLINE | ID: mdl-12857949

ABSTRACT

One hypothesis for the etiology of behavioral disorders is that infection by a virus induces neuronal cell dysfunctions resulting in a wide range of behavioral abnormalities. However, a direct linkage between viral infections and neurobehavioral disturbances associated with human psychiatric disorders has not been identified. Here, we show that transgenic mice expressing the phosphoprotein (P) of Borna disease virus (BDV) in glial cells develop behavioral abnormalities, such as enhanced intermale aggressiveness, hyperactivity, and spatial reference memory deficit. We demonstrate that the transgenic brains exhibit a significant reduction in brain-derived neurotrophic factor and serotonin receptor expression, as well as a marked decrease in synaptic density. These results demonstrate that glial expression of BDV P leads to behavioral and neurobiological disturbances resembling those in BDV-infected animals. Furthermore, the lack of reactive astrocytosis and neuronal degeneration in the brains indicates that P can directly induce glial cell dysfunction and also suggests that the transgenic mice may exhibit neuropathological and neurophysiological abnormalities resembling those of psychiatric patients. Our results provide a new insight to explore the relationship between viral infections and neurobehavioral disorders.


Subject(s)
Borna disease virus/pathogenicity , Neuroglia/physiology , Neuroglia/virology , Viral Proteins/physiology , Animals , Borna Disease/physiopathology , Borna Disease/psychology , Borna Disease/virology , Borna disease virus/genetics , Borna disease virus/physiology , Glial Fibrillary Acidic Protein/genetics , Humans , Male , Mental Disorders/etiology , Mental Disorders/pathology , Mental Disorders/virology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Neurological , Nervous System Diseases/etiology , Nervous System Diseases/pathology , Nervous System Diseases/virology , Phosphoproteins/genetics , Phosphoproteins/physiology , Viral Proteins/genetics
6.
Front Biosci ; 7: d593-607, 2002 Mar 01.
Article in English | MEDLINE | ID: mdl-11861216

ABSTRACT

Autism spectrum disorders (ASD) have been the focus of a great deal of research and clinical speculation. This intense interest relates to both the perplexing pathogenesis and devastating consequences of these disorders. One of the obstacles to understanding the pathogenesis of autism and its efficient treatment has been the paucity of animal models that could be used for hypotheses-driven mechanistic studies of abnormal brain and behavior development and for the pre-clinical testing novel pharmacological treatments. The present review provides a detailed analysis of a new animal model of ASD. This model utilizes neonatal Borna disease virus (BDV) infection of the rat brain as a unique experimental teratogen to study the pathogenesis of neurodevelopmental damage. For more than a decade, studies of the BDV animal model have yielded much insight into the pathogenic processes of abnormal brain development and resulting autistic-like behavioral abnormalities in rats. The most recent experiments demonstrate the utility of the BDV model for studying the pathophysiological mechanisms of the gene-environment interaction that determines differential disease outcomes and variability in responses to treatments.


Subject(s)
Animals, Newborn/psychology , Autistic Disorder/virology , Borna Disease/psychology , Borna Disease/virology , Borna disease virus/isolation & purification , Brain/growth & development , Brain/physiopathology , Disease Models, Animal , Animals , Animals, Newborn/virology , Autistic Disorder/physiopathology , Borna Disease/physiopathology , Brain/virology , Humans , Rats , Rats, Inbred Lew
8.
Eur Psychiatry ; 16(1): 3-10, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11246286

ABSTRACT

Borna disease virus (BDV), a noncytolytic neurotropic nonsegmented negative-stranded RNA virus with a wide geographic distribution, infects several vertebrate animal species and causes an immune-mediated central nervous system (CNS) disease with various manifestations, depending on both host and viral factors. In animal infections, BDV can persist in the CNS and induce alterations in brain cell functions, neurodevelopmental abnormalities and behavioral disturbances. An association between BDV and psychiatric disorders (essentially schizophrenia and affective disorders) has been suggested by some serologic and molecular studies but further investigations are required to substantiate the possible contribution of this virus to the pathogenesis of these disorders.


Subject(s)
Autistic Disorder/virology , Bipolar Disorder/virology , Borna Disease/psychology , Borna Disease/virology , Borna disease virus/isolation & purification , Brain/physiopathology , Brain/virology , Schizophrenia/virology , Borna Disease/metabolism , Borna disease virus/metabolism , Humans , RNA, Viral/metabolism
9.
Behav Brain Res ; 120(2): 189-201, 2001 May.
Article in English | MEDLINE | ID: mdl-11182167

ABSTRACT

Borna disease virus (BDV) is a highly neurotropic RNA virus that causes a CD8(+) T cell-mediated neurological disease in certain mouse strains. We established asymptomatic persistent central nervous system (CNS) infections in mutant C57BL/10J mice that lack functional CD8(+) T cells. When analyzed at adult age for spatial learning abilities in a water maze, BDV-infected mice showed slightly impaired escape performance while their exploratory behavior in an openfield test was indistinguishable from uninfected control mice. Histological and molecular biological analysis revealed extensive viral spread throughout the CNS of infected animals. Most neurons of the hippocampus contained viral antigen, but there was no overt loss of neurons from this structure. We found almost unchanged levels of the proinflammatory cytokines IL-1beta and TNF-alpha, but clearly increased levels of the chemokines IP-10 and RANTES in brains of infected mice. Re-examination of water maze data revealed that only infected mice with IP-10 transcript levels above a certain threshold showed impaired performance, whereas the performance of infected mice with lower IP-10 levels was indistinguishable from uninfected controls. This suggests that BDV infection can disturb the function of the mammalian CNS without causing overt neuronal loss, and that the magnitude of virus-induced chemokine production in the CNS correlates with the degree of impairment.


Subject(s)
Borna Disease/metabolism , Borna Disease/psychology , Borna disease virus , Central Nervous System Infections/metabolism , Central Nervous System Infections/psychology , Chemokines/biosynthesis , Learning Disabilities/psychology , Animals , Antineoplastic Agents/metabolism , Behavior, Animal/physiology , Biomarkers , Blotting, Northern , Borna Disease/complications , Chemokine CXCL10/biosynthesis , Exploratory Behavior/physiology , Immunohistochemistry , Learning Disabilities/etiology , Maze Learning/physiology , Memory/physiology , Mice , Mice, Inbred C57BL , RNA/biosynthesis , Ribonucleases/metabolism , Viral Load
10.
Lancet Infect Dis ; 1(1): 46-52, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11871411

ABSTRACT

Animals infected with Borna disease virus (BDV) typically present with neurological dysfunction including behavioural abnormalities. Seroepidemiological surveys suggested that BDV infection can occur in human beings and is associated with mental disorders. Partly contradictory results from studies employing RT-PCR and serological screening led to debate over whether BDV can infect people at all. Critical evaluation of available data led to doubts about the diagnostic value of RT-PCR-based test results. A more consistent picture has emerged from serological studies because seropositive cases were found more frequently among psychiatric patients than among normal controls, supporting the notion that BDV might indeed be responsible for some psychiatric disorders. This view is now challenged by the observation that human BDV-reactive antibodies are of low avidity and might therefore represent cross-reacting antibodies. It remains to be shown whether these antibodies are indeed induced by BDV or by related antigens of unknown identity.


Subject(s)
Borna Disease/complications , Mental Disorders/etiology , Animals , Antibodies, Viral/blood , Antibody Affinity , Borna Disease/diagnosis , Borna Disease/psychology , Borna disease virus/genetics , Borna disease virus/immunology , Borna disease virus/isolation & purification , Brain/virology , Humans , Mental Disorders/virology , RNA, Viral/analysis
11.
J Neurovirol ; 5(6): 604-12, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10602401

ABSTRACT

Although the question of human BDV infection remains to be resolved, burgeoning interest in this unique pathogen has provided tools for exploring the pharmacology and neurochemistry of neuropsychiatric disorders potentially linked to BDV infection. Two animal models have been established based on BDV infection of adult or neonatal Lewis rats. Analysis of these models is already yielding insights into mechanisms by which neurotropic agents and/or immune factors may impact developing or mature CNS circuitry to effect complex disturbances in movement and behavior.


Subject(s)
Borna Disease/immunology , Borna disease virus/pathogenicity , Central Nervous System Viral Diseases/physiopathology , Animals , Animals, Newborn , Antibody Formation , Apoptosis/immunology , Borna Disease/pathology , Borna Disease/psychology , Borna Disease/virology , Borna disease virus/physiology , Brain Chemistry , Central Nervous System Viral Diseases/pathology , Central Nervous System Viral Diseases/virology , Disease Models, Animal , Dopamine/physiology , Humans , Immunity, Cellular , Locomotion , Rats , Rats, Inbred Lew , Virus Latency
12.
Brain Res Bull ; 48(1): 23-30, 1999 Jan 01.
Article in English | MEDLINE | ID: mdl-10210164

ABSTRACT

In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. In this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density.


Subject(s)
Borna Disease/pathology , Borna Disease/psychology , Dentate Gyrus/pathology , Maze Learning/physiology , Memory Disorders/etiology , Animals , Borna Disease/complications , Rats , Rats, Inbred Lew , Swimming
14.
15.
Pharmacopsychiatry ; 31(3): 77-82, 1998 May.
Article in English | MEDLINE | ID: mdl-9657234

ABSTRACT

Borna Disease Virus (BDV) infections are widespread in animal species. This neurotropic, negative and single-stranded enveloped RNA virus spreads via axonal and transsynaptic pathways quite specifically into olfactoric and limbic structures. The symptoms in BDV-infected animals range from unapparent or subtle clinical manifestations to fatal neurological disorders. The severe and fulminant course of the infection, which is often accompanied by neurobehavioral and "emotional" disturbances, occurs sporadically and, at least in experimentally infected animals (rats), is thought to be mediated by immunopathology. Increases in serum-BDV antibodies have also been detected in neuropsychiatric patients. In addition, viral antigen and viral RNA have been observed in acutely ill major depressive patients, leading to the conclusion that BDV was causally related to psychiatric disorders, in particular to affective disorders. A number of studies have meanwhile furnished evidence of abnormal immune functions in mentally ill patients. In addition, stress has been shown to decrease immune responses to viral infections. On the basis of these findings it is hypothesized that human BDV infection represents a co-factor in the development or course of psychiatric diseases. Stress may cause immunosuppression and thus induce activation of persisting BDV in the limbic system, resulting in an inflammatory reaction of these structures. These neuropathological changes might influence the serotonergic or dopaminergic neurotransmitter systems. In addition, a specific affinity of BDV structural elements for aspartate and glutamate receptors in the hippocampal formation might directly induce an imbalance of these transmitter system interactions, causing affective and behavioral disturbances. The possible interactions between stress-induced immunosuppression, BDV infection and affective disorders in humans, and the theoretical and clinical aspects of this concept are discussed.


Subject(s)
Borna Disease/psychology , Borna Disease/virology , Borna disease virus , Mood Disorders/psychology , Mood Disorders/virology , Animals , Borna Disease/immunology , Humans , Mood Disorders/immunology
16.
Neuropsychobiology ; 37(2): 59-64, 1998.
Article in English | MEDLINE | ID: mdl-9566266

ABSTRACT

The relationship between Borna disease virus (BDV) infection and positive and negative syndromes in schizophrenia was investigated. By nested RT-PCR and Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in blood from 67 schizophrenic patients (DSM-III-R) in Japan, and the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) were analyzed. There were significant (p < 0.05) differences in the composite index denoting the positive minus negative difference indicating a dominant contribution by negative items, and the proportion of negative type (positive minus negative value below zero) patients, between patients positive and negative for anti-BDV p24 antibodies. It is possible that BDV infection with induction of BDV p24 antibodies may be associated with negative syndromes in schizophrenic patients.


Subject(s)
Borna Disease/psychology , Schizophrenia/complications , Schizophrenic Psychology , Adult , Borna Disease/complications , Borna disease virus/metabolism , Chronic Disease , Female , Humans , Japan , Length of Stay , Male , Polymerase Chain Reaction , Psychiatric Status Rating Scales , RNA, Viral/analysis , RNA, Viral/chemistry
17.
Pharmacol Biochem Behav ; 59(4): 1047-52, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9586866

ABSTRACT

Borna disease virus (BDV) is a neurotropic RNA virus that infects warm-blooded animals to cause disturbances of movement and behavior. Studies in infected rats have demonstrated behavioral sensitivity to direct and indirect dopamine (DA) agonists; however, behavioral responses to an indirect DA agonist with a pure presynaptic effect have not been analyzed. Rats infected with BDV had an enhanced response to the locomotor, behavioral, and convulsant effects of cocaine at intraperitoneal doses of 7.5, 15, and 30 mg/kg. The basis for this sensitivity was examined by striatal DA uptake site and D1 and D2 receptor autoradiography. DA uptake sites, labeled with [3H] mazindol, were reduced in medial caudate-putamen (CP), and binding of [3H] raclopride to D2 sites was reduced in medial and ventral striatal areas. The topography of DA uptake and D2 site loss corresponds to the distribution of BDV viral nucleic acids in CP and overlays the medial striatal areas that function in conditioned reward. The BDV-infected rat provides a model of cocaine sensitivity based on viral central nervous system infection and may have relevance for studies of cocaine abuse in the context of other viral encephalopathies, such as those associated with HIV infection.


Subject(s)
Borna Disease/psychology , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Animals , Autoradiography , Behavior, Animal/drug effects , Caudate Nucleus/drug effects , Caudate Nucleus/metabolism , In Situ Hybridization , Male , Mazindol/pharmacology , Motor Activity/drug effects , Putamen/drug effects , Putamen/metabolism , Rats , Rats, Inbred Lew
18.
Tierarztl Prax ; 23(3): 207-16, 1995 Jun.
Article in German | MEDLINE | ID: mdl-7676427

ABSTRACT

Borna disease has a 230 year old history, having first been described in 1766. Scientific studies of borna disease began in 1895. Ernst Joest and Kurt Degen found inclusion bodies within ganglion cells of the hippocampus in 1909. Wilhelm Zwick successfully transmitted Borna disease to rabbits in 1924. This marked the beginning of systematic studies to determine the pathogenesis of Borna disease as it is now understood in the 1990s.


Subject(s)
Borna Disease/history , Borna Disease/physiopathology , Horse Diseases , Animals , Borna Disease/psychology , Borna disease virus/isolation & purification , Germany , Hippocampus/pathology , Hippocampus/virology , History, 18th Century , History, 19th Century , History, 20th Century , Horses , Inclusion Bodies/ultrastructure
20.
Nervenarzt ; 65(3): 169-74, 1994 Mar.
Article in German | MEDLINE | ID: mdl-8177357

ABSTRACT

There is growing evidence, that Borna Disease virus (BDV) or a variant may cause neuropsychiatric disorders in humans. The presence of specific BDV serum antibodies indicates an earlier contact with BDV. Earlier MRI results showing a raised prevalence of white matter lesions in BDV-seropositive psychiatric patients, possibly indicating encephalitic lesions, are not confirmed in this extended study, however in BDV-seropositive psychiatric patients the occurrence of cerebral atrophy seems to be more frequent, a finding compatible with hydrocephalus e vacuo found in animals after BDV-encephalitis. Because encephalitic lesions in BD are predominantly found in the gray matter of the brain, which is hardly visualized by MRI, the failure to detect lesions in BDV-seropositive patients could be due to methodological problems.


Subject(s)
Antibodies, Viral/blood , Borna Disease/diagnosis , Borna disease virus/immunology , Encephalitis/diagnosis , Neurocognitive Disorders/diagnosis , Adult , Aged , Atrophy , Borna Disease/immunology , Borna Disease/psychology , Brain/pathology , Encephalitis/immunology , Encephalitis/psychology , Female , Humans , Male , Middle Aged , Neurocognitive Disorders/immunology , Neurocognitive Disorders/psychology
SELECTION OF CITATIONS
SEARCH DETAIL
...