Autoimmunity in schizophrenia: culprit or bystander?

Abstract

In chapter 1 an overview of the literature that links schizophrenia and the immune system is given. Previous studies have reported an increased prevalence of antinuclear antibodies in patients with schizophrenia. In chapter 2 the prevalence of antinuclear antibodies was measured in 368 patients with schizophrenia and 283 healthy controls. In conclusion, no association was found between the presence of these antibodies and schizophrenia. Laboratory investigations in patients with a psychotic disorder could be of aid in detecting relevant co-morbid disorders or cases of psychosis due to a general medical condition. The retrospective study in chapter 3 describes the results of 23 tests conducted in a cohort of 215 patients with a psychotic disorder. These routine laboratory investigations did not result in the identification of cases of psychosis due to a general medical condition or in any relevant alterations in clinical care. Pathogens that are capable of infecting the central nervous system have been suggested as a potential environmental risk factor for schizophrenia. Chapter 4 describes the results of examining the seroprevalence and titer of IgG antibodies against herpes simplex virus-1 and -2 (HSV-1/HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Toxoplasma gondii (TG) in plasma of 368 adult patients with schizophrenia and 282 controls. Results show a slightly higher seroprevalence of VZV and CMV in controls. No significant differences were found in the seroprevalence of the other pathogens. In chapter 5 an overview of the studies on the role and functioning of B-cells in schizophrenia is given, as results from the largest genome wide association study on schizophrenia suggest that these cells might be involved in the pathogenesis of schizophrenia. Anti-NMDA receptor encephalitis can present with severe psychiatric symptoms and is sometimes misdiagnosed as psychosis or mania. The results of routinely screening for antibodies against the GluN1 subunit of the NMDA-receptor in patients admitted to a first-episode psychosis clinic are described in chapter 6. In total 127 patients were screened of which 0 tested positive for these antibodies. In addition to this, three cases of patients with anti-NMDA receptor encephalitis with an onset with severe psychiatric symptoms are described. Chapter 7 describes the results of screening for GluN1 antibodies in 3 cohorts of patients with psychotic symptoms. In total, 475 patients were included and the cohorts consisted of patients with a first episode psychosis and patients with schizophrenia. Results showed 2 cases that tested positive for GluN1 antibodies, using a cell-based assay, but these findings could not be validated using immunohistochemistry. These results do not suggest that a significant subpopulation of patients with schizophrenia have an unrecognized form of anti-NMDA receptor encephalitis. In chapter 8 an effort is made to examine the relevance of other anti-neuronal membrane antibodies in patients with schizophrenia. Plasma samples of 104 patients were screened for such antibodies. None of the included samples showed positive results. These results suggest that anti-neuronal membrane antibodies do not play a major role in the pathogenesis of schizophrenia.