A VIRO-PSYCHO-IMMUNOLOGICAL DISEASE-MODEL OF A SUBTYPE AFFECTIVE-DISORDER

Borna Disease Virus (BDV) infections are widespread in animal species. This neurotropic, negative and single-stranded enveloped RNA virus sp reads via axonal and transsynaptic pathways quite specifically into ol factoric and limbic structures. The symptoms in BDV-infected animals r ange from unapparent or subtle clinical manifestations to fatal neurol ogical disorders. The severe and fulminant course of the infection, wh ich is often accompanied by neurobehavioral and ''emotional'' disturba nces, occurs sporadically and, at least in experimentally infected ani mals (rats), is thought to be mediated by immunopathology. Increases i n serum-BDV antibodies have also been detected in neuropsychiatric pat ients. 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 af fective disorders. A number of studies have meanwhile furnished eviden ce of abnormal immune functions in mentally ill patients. In addition, stress has been shown to decrease immune responses to viral infection s. On the basis of these findings it is hypothesized that human BDV in fection represents a co-factor in the development or course of psychia tric diseases. Stress may cause immunosuppression and thus induce acti vation of persisting BDV in the limbic system, resulting in an inflamm atory reaction of these structures. These neuropathological changes mi ght influence the serotonergic or dopaminergic neurotransmitter system s. In addition, a specific affinity of BDV structural elements for asp artate and glutamate receptors in the hippocampal formation might dire ctly induce an imbalance of these transmitter system interactions, cau sing 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.