Autoimmunity in Schizophrenia: A Review of Recent Findings
University of Pittsburgh Medical School, Department of Psychiatry, Pennsylvania 15213.Annals of Medicine (Impact Factor: 3.89). 11/1993; 25(5):489-96. DOI: 10.3109/07853899309147317
The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.
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- "This, together with other evidence implicating the HLA DRB1 locus as being associated with risk for schizophrenia and autism, may support the notion for a role for neuroinflammation and possibly autoimmunity in neuropsychiatric disorders (Crespi and Thiselton, 2011). Association with HLA antigens in schizophrenia had been noted before and different authors had already speculated some 20 years ago toward the existence of subgroups of schizophrenics who have immunological abnormalities like antinuclear antibodies in lupus erythematosus, known as neuropsychiatric lupus (Ganguli et al., 1993). "
ABSTRACT: Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the central nervous system, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand-activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.
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- "In fact, for schizophrenia, a neuroimmune hypothesis has been debated for decades , most recently in terms of NMDA-receptor autoimmunity [85, 86]. Although the current consensus concerning the inflammatory etiology of schizophrenia involves the idea of a long-lasting consequence of an infective-immune challenge during early brain development, numerous other explanations have been offered, including autoimmunity towards certain brain structures , particularly in the hippocampus . However, as inflammation is also closely linked with behavioral parameters such as exercise, alcohol abuse, and smoking, as well as with medical conditions including coronary artery disease, obesity, and insulin resistance , interpreting the inflammatory findings in psychiatric disease is exceedingly complex. "
ABSTRACT: Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as both a matrix protein and a cell-surface receptor. It is particularly copious in the skin, where it is known to be a structural component of hemidesmosomes. In addition, collagen XVII has been found to be present in the central nervous system, thus offering an explanation for the statistical association between bullous pemphigoid, in which autoimmunity is directed against dermal collagen XVII, and neurological diseases. In support of the hypothesis that collagen XVII serves as a shared antigen mediating an immune response between skin and brain, research on animal and human tissue, as well as numerous epidemiological and case studies, is presented.
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- "Several studies have pinpointed that schizophrenia has an autoimmune background. Autoimmunity was suspected mainly because: (1) patients with a schizophrenic first degree relative were significantly more likely to also have a parent or sibling with insulin dependent diabetes mellitus or other autoimmune disorders (Wright et al., 1996); (2) increased serum level of autoantibodies and other immunological abnormalities (review by Ganguli et al., 1993); (3) the demonstration of geographical concurrence of high rates of schizophrenia and flavivirus infections (Rubinstein, 1997); and (4) reports of an association of the disease with HLA class II alleles (Wright et al., 2001). Interestingly, however, there seems to be a strong negative correlation between schizophrenia and rheumatoid arthritis (Rubinstein, 1997). "
ABSTRACT: An overactivation of the Th1 activity in schizophrenia had been described. Interleukin-12 (IL-12), a proinflammatory cytokine, plays a key role in the regulation of the Th1 response. The aims of this study were to investigate the effect of first and second generation antipsychotic drugs on IL-12 production during the acute phase of the illness and its association with clinical features. Participants comprised 56 drug-naïve first episode psychotic patients and 28 healthy volunteers. Patients were initially randomly assigned to risperidone (n=16), olanzapine (n=20) or haloperidol (n=20); subject were maintained on the same medication throughout the study. Clinical assessments were conducted at baseline and at 6 weeks. IL-12 plasma levels were assessed at baseline and after 6 weeks of antipsychotic treatment. IL-12 haplotypes were also analysed. Patients showed higher IL-12 plasma levels at baseline compared with controls, and had a significant increase in IL-12 plasma level after 6 weeks of antipsychotic treatment. No significant differences in IL-12 level increase were found among the three antipsychotic treatments. IL-12 plasma levels at week 6 were not significantly associated with the severity of psychopathology at week 6. Thus, patients with a first episode of psychosis have inflammatory-like immunological function during early phases of the illness that it is independent of the antipsychotic treatment used.
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