This is a proposal to investigate the hypothesis that an autoimmune process directed against brain tissue antigens might be causally related to the production of psychotic symptoms in schizophrenics. The plan to test this hypothesis is characterized by two approaches: 1) a cross-sectional study of multiple immunologic parameters in acutely psychotic schizophrenic patients, psychotic patients with Systemic Lupus Erythematosus (SLE) contrasted with schizophrenics in remission, previously unmedicated schizophrenics, nonpsychotic SLE patients, brain damaged non-psychotic patients and normal controls. This part of the investigation will show if there is a specific association between psychotic symptoms and an autoimmune anti-brain response. 2) A longitudinal follow up of the schizophrenic patients will then be carried out with frequent repeated measurements of immunologic parameters and of the level of psychotic symptomatology. This part of the investigation will reveal if the autoimmune phenomena and the level of psychotic symptoms covary and whether the autoimmune phenomena emerge before corresponding changes in clinical state. The design of the study has been derived from current models of immunopathophysiology in known autoimmune disorders such as SLE, Insulin Dependent Diabetes Mellitus and autoimmune hyperthyroidism. This study promises to answer in a definitive way questions raised by pilot data gathered by the Principal Investigator and by other studies over the last 30 years which have demonstrated an association between immune dysfunction and schizophrenia. Uncovering an autoimmune pathogenesis in even a subgroup of schizophrenics would lead to further studies of etiology in schizophrenia and also open the door to a number of novel treatment approaches based on modifying the immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041883-02
Application #
3380800
Study Section
(PCBB)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Nimgaonkar, V L; Zhang, X R; Brar, J S et al. (1996) 5-HT2 receptor gene locus: association with schizophrenia or treatment response not detected. Psychiatr Genet 6:23-7
Nimgaonkar, V L; Sanders, A R; Ganguli, R et al. (1996) Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples. Am J Med Genet 67:505-14
Nimgaonkar, V L; Yang, Z W; Zhang, X R et al. (1995) Association study of schizophrenia and the IL-2 receptor beta chain gene. Am J Med Genet 60:448-51
Nimgaonkar, V L; Zhang, X R; Brar, J S et al. (1995) Lack of association of schizophrenia with the neurotrophin-3 gene locus. Acta Psychiatr Scand 92:464-6
Ganguli, R; Brar, J S; Chengappa, K R et al. (1995) Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms. Arch Gen Psychiatry 52:668-72
Chengappa, K N; Nimgaonkar, V L; Bachert, C et al. (1995) Obstetric complications and autoantibodies in schizophrenia. Acta Psychiatr Scand 92:270-3
Chengappa, K N; Ganguli, R; Yang, Z W et al. (1995) Impaired mitogen (PHA) responsiveness and increased autoantibodies in Caucasian schizophrenic patients with the HLA B8/DR3 phenotype. Biol Psychiatry 37:546-9
Yang, Z W; Chengappa, K N; Shurin, G et al. (1994) An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia. Psychol Med 24:449-55
Ganguli, R; Yang, Z; Shurin, G et al. (1994) Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Res 51:1-10
Silver, M A; Yang, Z W; Ganguli, R et al. (1994) An inhibitory effect of psychoactive drugs on a human neuroblastoma cell line. Biol Psychiatry 35:824-6

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