This is a competitive renewal application for an ongoing project aimed at testing the hypothesis that an autoimmune process directed against brain antigens is involved in the etiology or pathogenesis of psychotic symptoms in a subgroup of schizophrenics patients. During the 2 years so far funded, 118 schizophrenic patients and 96 controls have been studied cross-sectionally. Preliminary data show that 31% schizophrenics fall into an immunologically abnormal subgroup who can be immunologically distinguished from normal controls and immunologically normal schizophrenics. Extensive developmental work has also been carried out on the detection of circulating specific antibrain immunoglobulin and anti-brain cell-mediated immunologic responses. Preliminary results using these methods suggest that there is an increased mitotic stimulation of lymphocytes by brain antigens and specific immunoglobulins binding to these antigens in some schizophrenics. During the period of this renewal, recruitment of the cross-sectional portion of the study will be completed to include 180 schizophrenics (including 60 never-medicated patients) and 30 non-psychotic, brain damaged individuals. A longitudinal study of 40 immunologically abnormal and 40 immunologically normal schizophrenic patients will also begin. Each patient will be followed for one year with weekly ratings of clinical state and monthly immunologic assessments. During exacerbations of psychotic symptoms, immunologic tests will be done weekly. If autoimmune mechanisms play a role in the pathogenesis of psychotic symptoms in the immunologically abnormal patients, then clinical and immunologic state measures will be predicted to covary over time only in that subgroup. Furthermore, in the immunologically abnormal subgroup, changes in some immunologic measures may temporally precede the worsening of psychotic symptoms. This is the first multidimensional investigation of the autoimmune hypothesis in schizophrenia and the first attempt to study immunologic phenomena in schizophrenic patients longitudinally.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041883-06
Application #
2245299
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1986-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1995-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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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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