Infection and autoimmunity as etiologic factors in schizophrenia: a review and reappraisal.
The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. One etiologic hypothesis is that schizophrenia is the result of an infection (especially by a virus) or of an autoimmune reaction (perhaps following an infection) against central nervous system (CNS) tissue. Indirect evidence supporting this hypothesis includes possible geographic variance in the prevalence of schizophrenia, a season-of-birth effect, and observed associations between schizophrenia and prenatal exposure to viral epidemics. Several studies of cell-based and humoral immunity, as well as studies of cytokines, have indicated abnormalities in the immune function of schizophrenia patients, but many of these findings have not been replicated consistently. In addition, most observed alterations in immune function have been modest in degree and nonspecific. Attempts to identify a specific infectious agent or an antibody directed against CNS tissue have not produced a consistently replicable finding. In summary, no research evidence to date irrefutably indicates an infectious or autoimmune etiologic process in schizophrenia. It is probably unreasonable, however, to view schizophrenia as having a single cause. It is much more likely to be a heterogeneous disorder resulting from interactions between multiple factors, including the person's genetic endowment and various environmental influences. Infectious agents or CNS autoantibodies may well be among these environmental variables. A major current emphasis is on studying potential interactions between exposure to an infection or an autoimmune response and key early phases of brain development. A corresponding priority in the research agenda will be the development of animal models of CNS development that might elucidate the pathogenic mechanisms of such an interaction.
Kirch
D G
DG
National Institutes of Health, Bethesda, MD 20892.
D015551:Autoimmunity; D006801:Humans; D007239:Infections / Q000150:complications*; D012559:Schizophrenia / Q000209:etiology* / Q000276:immunology; D014777:Virus Diseases / Q000150:complications