Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder

Abstract

In 1983, reports of antibodies in subjects with major depressive disorder to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to the molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV).1,2 This advance enabled the development of new diagnostic assays including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990 more than 80 studies have reported an association between BDV and a wide range of human illnesses that include major depressive disorder, bipolar disorder, schizophrenia, anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme.3,4 However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serologic and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially-collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 schizophrenia/control pairs, 66 bipolar disorder/control pairs, and 80 major depressive disorder/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.

Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother

“…Although Borna disease virus (BDV) is a prototypical mammalian bornavirus that causes neurobehavioral disorders in rodents (1), the association between BDV and human psychiatric disorders remains controversial (2). Recently, bornaviruses related to BDV were discovered in birds (i.e., avian bornaviruses) (3).…”

“…However, inter-laboratory variations in assessing epidemiological assay results have led to inconsistent findings regarding the bornavirus prevalence (5). Overcoming this situation is the first step of reevaluation of bornavirus surveys; therefore, we designed a diagnostic procedure for evaluating bornavirus epidemiology as follows: first, the presence of BDV-reactive antibodies is evaluated by using an indirect immunofluorescence assay (IFA), the most reliable assay for detecting these antibodies (2,5). Second, BDV-reactive samples are evaluated to confirm the presence of antibodies against linear and conformational BDV epitopes by using Western blotting (WB) and a radioligand assay (RLA), respectively (6).…”

Epidemiology and host spectrum of Borna disease virus infections

“…The situation is even more complicated by the facts that no consensus exists on the method that should be used for BDV diagnosis (Wolff et al and that, based on sequence identity, many PCR results and even virus isolation from human peripheral blood cells have been suspected to have arisen from contamination by a control strain (Lieb et al, 1997;Schwemmle et al, 1999;Planz et al, 2003;reviewed by Sauder et al, 2002;Dürrwald et al, 2006b). A recent study using extremely tight criteria for BDV positivity found neither BDV RNA nor verifiable BDV antibodies in the blood samples of Californian psychiatric patients (Hornig et al, 2012).…”

The game's afoot: seeking viruses that cause chronic and degenerative neurologic and psychiatric disorder

“…3 To evaluate whether such hormonal, immunological or neuropsychiatric disorders were associated with a persistent viral infection(s) required an armamentarium of novel and sophisticated approaches and techniques to uncover viral genes and/or viral gene products, and discriminate those findings from normal host genes and their products. This issue's paper from Ian Lipkin's laboratory, 'Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder,' by Hornig et al 4 displays the usage of such an approach and the controls required to critically define or refute that a pathogen is the cause of a chronic psychiatric disorder.…”