Immune abnormalities in schizophrenia: evidence for the autoimmune hypothesis

The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross-referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin-2, and increased serum concentrations of interleukin-2 receptor and interleukin-6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug-naive patients.