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 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.