Autoimmunity in Schizophrenia: A Review of Recent Findings

University of Pittsburgh Medical School, Department of Psychiatry, Pennsylvania 15213.
Annals of Medicine (Impact Factor: 4.73). 11/1993; 25(5):489-96. DOI: 10.3109/07853899309147317
Source: PubMed

ABSTRACT 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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    • "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). "
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    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.
    Psychiatry Research 04/2008; 158(2):206-16. DOI:10.1016/j.psychres.2006.08.005 · 2.68 Impact Factor
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    • "The presence of immunological abnormalities in schizophrenic patients has been widely reported (Ganguli et al. 1993, 1994; Kolyaskina et al. 1998, 1999, 2004; Muller et al. 2000). Replicated immune abnormalities in schizophrenic patients include a decrease of cellular branch and prevalence of humoral branch of immunity, especially the increased production of antinuclear antibodies, antiphospholipid antibodies, antibodies to cardiolipin, DNA, and myelin basic protein (Ganguli et al. 1992, 1994; Sirota et al. 1993; Spivak et al. 1995; Kolyaskina et al. 2004). "
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    ABSTRACT: Replicated abnormalities in schizophrenia include decreased cellular immunity. The aim of the study was to verify whether there are some abnormalities in the ultrastructure of lymphocytes in drug-free schizophrenic patients. Fifty-nine in-patients with paranoid schizophrenia (DSM-IV 295.30) and 31 normal controls were used. Psychosis severity was assessed by the PANSS psychotic cluster. Electron microscopy and morphometric methods were applied to estimate the frequency and ultrastructural parameters of small, large, large activated lymphocytes (LAL) (containing 10 and more mitochondria) and of atypical lymphocytes (lymphoblasts, LB). The frequency of small lymphocytes in schizophrenic patients was lower and that of large lymphocytes, LAL and LB was higher than in controls (all p= < 0.01). The volume density (Vv) of mitochondria in LAL in individuals with schizophrenia was lower than in controls (p<0.05), correlated negatively with the frequency of LB, Vv and number of lysosomes in LB (all p<0.01) and with the psychosis severity (p<0.05). In schizophrenic patients a trend towards positive correlations between the frequency of LB and psychosis severity were found (p<0.07). The data suggest that the excess of LB in schizophrenic patients is associated with the dysfunction of energy metabolism in LAL, and these abnormalities are related to schizophrenia.
    The World Journal of Biological Psychiatry 02/2007; 8(1):30-7. DOI:10.1080/15622970600960207 · 4.23 Impact Factor
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    • "In the last two decades, however, a revolution in the biomedical technologies equipped scientists with powerful research tools, facilitating rapid progress in the field of psychoneuroimmunology. Application of these methods actuated a series of studies that shed new light on the pathogenesis and pathophysiology of some psychiatric disorders, e.g., schizophrenia (Ganguli et al., 1993; Kronfol and Remick, 2000; Schuld et al., 2004), obsessive-compulsive disease (Cazzullo et al., 2003), major depression (O'Brien et al., 2004; Schiepers et al., 2005), etc. Alongside the widely accepted dopamine theory (Cohen and Servan- Schreiber, 1993), several other hypotheses have been suggested. A potential involvement of immune mechanisms in the etiopathogenesis of schizophrenia has been considered (Rothermundt et al., 2001). "
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    ABSTRACT: Growing evidence suggests that the immune, endocrine, and nervous systems interact with each other through cytokines, hormones, and neurotransmitters. The activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous system (CNS) of schizophrenic patients. Numerous studies report that treatment with antipsychotic drugs affects the cytokine network. Hence, it is plausible that the influence of antipsychotics on the cytokine systems may be responsible for their clinical efficacy in schizophrenia. This article reviews current data on the cytokine-modulating potential of antipsychotic drugs. First, basic information on the cytokine networks with special reference to their role in the CNS as well as an up-to-date knowledge of the cytokine alterations in schizophrenia is outlined. Second, the hitherto published studies on the influence of antipsychotics on the cytokine system are reviewed. Third, the possible mechanisms underlying antipsychotics' potential to influence the cytokine networks and the most relevant aspects of this activity are discussed. Finally, limitations of the presented studies and prospects of future research are delineated.
    Brain Behavior and Immunity 12/2006; 20(6):532-45. DOI:10.1016/j.bbi.2006.02.002 · 6.13 Impact Factor
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