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Schizophrenia and epilepsy: clinical and pathological studies
373 whether neuroleptic effects may have accounted for these differences, skin biopsies from 4 normals were treated in culture with haloperidol at doses varying from 5 ng to 5 pg per ml in tissue culture medium, and periods varying from 1 to 4 weeks. In no case did this result in an abnormal initial growth or doubling time, as seen in the patients. Further, initial growth and doubling time did not differ between the group of 4 patients who had been off neuroleptics for at least 4 weeks at the time of biopsy and those who were receiving neuroleptics, and time to appearance of initial growth was delayed beyond two weeks in fibroblasts from two first-break drug-naive schizophrenic patients. More striking than the growth abnormalities were the morphological ?.. differences. hibrobiasts from patients showed random size, were mostiy aspiny or with short stubby projections, and had an irregular orientation with poor attachment. These abnormalities were also seen in fibroblasts from patients that showed normal initial growth and doubling time. All fibroblasts from normal controls showed the expected parallel alignment of normal diploid spindle-shaped cells. The potential implications of these findings and the potential for using skin fibroblasts as a cell model in schizophrenia research will be discussed. Additional findings will be presented from ongoing studies of fibronectin immunocytochemistry in these fibroblasts.
Increased percentages patients C.G. McAllister*,
of T lymphocytes
E. Konicki, D.G. Kirch, M.H. Rapaport,
in the CSF of schizophrenic S.M. Paul, D. Pickar
Department of Psychiatry, University of Pittsbwgh, CLSI (Immunopathology), Presbyterian UniversityHospital, DeSoto at O’Hara Street, Pittsburgh, PA 15213-2582, USA.
Abnormalities in the immune system of schizophrenic patients have been described by several groups. Most of these studies have examined the peripheral blood lymphocytes as representative of the immune status of the individual patient. In order to examine the lymphocytes that are potentially more closely associated with the brain, we determined by FACS analysis the subsets of lymphocytes present in the CSF of schizophrenic patients and control subjects. Forty milliliters of CSF were obtained by lumbar puncture (non-traumatic) and the last 4 milliliters were retained for subset analysis. The cells were washed and stained with the appropriate monoclonal antibody: anti-Leu 1, all T lymphocytes; anti-Leu 2, suppressor/cytotoxic T lymphocytes; anti-Leu 3, helper/inducer T lymphocytes; anti-Leu 12, all B lymphocytes; anti-HLA-DR, class II antigens. A minimum of 100 cells with lymphoid light scattering properties were examined. Results of 20 medicated schizophrenic patients demonstrate increased percentages of 1) total T cells (F = 17.9, p = 0.0002); 2) suppressor/cytotoxic T cells (F = 7.9, p = 0.009) and 3) helper/inducer T cells (F = 8.7, p = 0.0065) as compared to 10 control subjects. No differences in either B cell percentages (including the CD5 + B lymphocyte) or HLA-DR expression were observed suggesting that neuroleptic medication did not have a generalized effect on the percentages of lymphocytes in the CSF. Similar studies in never medicated schizophrenic patients are necessary to evaluate the contribution of anti-psychotic agents to the above results.
Schizophrenia
and epilepsy: clinical and pathological
studies
J.R. Stevens*, C.J. Bruton, C.D. Firth Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeth’s Hospital, Washington, DC 20032, USA.
The relationship between epilepsy, particularly temporal lobe epilepsy, and schizophrenia has long been of interest to investigators of both illnesses. With the goal of delineating anatomic sites of neuropathology and pertinent clinical data in individuals with epilepsy and a schizophrenia-like illness, clinical histories, EEG and brain pathology were examined for 13 individuals with a diagnosis of epilepsy plus schizophrenia during life compared with 37 individuals with a diagnosis of epilepsy but no psychosis. Patients diagnosed with epilepsy plus schizophrenia were all hospitalized and died at the Runwell Hospital, Essex, U.K., and were selected following review of the clinical records from a total of 651 patients with epilepsy, excluding material from patients with other psychoses, brain tumor, hemorrhage, Alzheimer’s disease, Huntington’s chorea, or postleukotomy seizures. Mean age at death of the 13 patients diagnosed with both epilepsy and schizophrenia was 67.5 years. Brain specimens from non-psychotic patients with epilepsy were from two sources: 1) individuals
374 whose epilepsy was so severe or whose family resources were so limited as to require the patient’s full time residency in an epileptic colony (n = 21; mean age at death 61.5 years); 2) individuals with epilepsy who were living and, in most cases, working in the community prior to death (n = 16, mean age 45.6 years). All brains were examined at the Runwell Hospital neuropathology laboratory where they were weighed, photographed and preserved in 10% formalin. Standard blocks and sections were prepared for histopathologic examination. Mean ages of onset of epilepsy differed between the three groups; community patients 23 years; schizophrenics 15.7 years; epileptic colony 6 years, but with a very wide variation for all three groups. Two schizophrenic patients developed the psychosis before the epilepsy; one coincident with epilepsy. Among the 10 others, onset of the chronic schizophrenia-like illness occurred 3 - 38 years after onset of epilepsy (mean 21.8 years). Differences in types of epilepsy, personal and family history and pathologic findings among the three groups are compared to delineate clinical and neuropathologic factors significantly related to development of a schizophrenia-like psychosis in individuals with epilepsy. Research supported by the Stanley Foundation, U.S.A.
Borna disease virus and schizophrenia: R.W. Waltrip*,
R.W. Buchanan,
K.M. Carbone,
Preliminary
results
A. Breier, 0. Narayan, W.T. Carpenter
Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD 21228, USA.
Viral and immunological etiological hypotheses in schizophrenia are considered attractive because they can account for a diverse range of manifestations. However, studies have yielded few specific findings, and no consistent associations with common CNS viruses. Preliminary data from an ongoing study of antibodies to Borna Disease Virus (BDV) antigen in patients referred to a research clinic with a presumptive diagnosis of schizophrenia indicates that: (1) nine of 49 patients (18%) have IgG antibodies to BDV and (2) the antibodies from the patients recognize the same intracellular antigen in a BDV-infected cell line as antibodies from a rabbit with BDV encephalitis. BDV is a highly neurotropic agent whose only known natural hosts are horses and sheep in central Europe. BDV is studied as a laboratory model of CNS-virus induced behavioral abnormalities. It has an extremely wide experimental host range, including avians, rodents, and primates. The manifestations of the disease depend upon the strain of virus and the species of host, ranging from asymptomatic infection through chronic forms to an acute fatal meningoencephalitis. BDV is exclusively neurotropic in adult animals, has a predilection for limbic structures and produces an immunopathological disease. Recent studies for the presence of antibodies to BDV in humans in the U.S. and Europe with psychiatric disease and neurological disease have been stimulated by observations of the behavioral abnormalities in animals. A seroprevalence ranging from 2 to 13% of antibodies to BDV in different populations has been observed. We are approaching this issue by screening schizophrenic patients for antibodies to BDV and characterization of seropositive individuals. A discussion of the biology of BDV with a focus on recent findings in animal models and observations in human populations will be presented. Screening and confirmation methods using single and double indirect immunofluorescence as well as clinical and MRI imaging findings contrasting seropositive and seronegative patients in our studies will be presented.
Increased percentages patients C.G. McAllister*,
of T lymphocytes
E. Konicki, D.G. Kirch, M.H. Rapaport,
in the CSF of schizophrenic S.M. Paul, D. Pickar
Department of Psychiatry, University of Pittsbwgh, CLSI (Immunopathology), Presbyterian UniversityHospital, DeSoto at O’Hara Street, Pittsburgh, PA 15213-2582, USA.
Abnormalities in the immune system of schizophrenic patients have been described by several groups. Most of these studies have examined the peripheral blood lymphocytes as representative of the immune status of the individual patient. In order to examine the lymphocytes that are potentially more closely associated with the brain, we determined by FACS analysis the subsets of lymphocytes present in the CSF of schizophrenic patients and control subjects. Forty milliliters of CSF were obtained by lumbar puncture (non-traumatic) and the last 4 milliliters were retained for subset analysis. The cells were washed and stained with the appropriate monoclonal antibody: anti-Leu 1, all T lymphocytes; anti-Leu 2, suppressor/cytotoxic T lymphocytes; anti-Leu 3, helper/inducer T lymphocytes; anti-Leu 12, all B lymphocytes; anti-HLA-DR, class II antigens. A minimum of 100 cells with lymphoid light scattering properties were examined. Results of 20 medicated schizophrenic patients demonstrate increased percentages of 1) total T cells (F = 17.9, p = 0.0002); 2) suppressor/cytotoxic T cells (F = 7.9, p = 0.009) and 3) helper/inducer T cells (F = 8.7, p = 0.0065) as compared to 10 control subjects. No differences in either B cell percentages (including the CD5 + B lymphocyte) or HLA-DR expression were observed suggesting that neuroleptic medication did not have a generalized effect on the percentages of lymphocytes in the CSF. Similar studies in never medicated schizophrenic patients are necessary to evaluate the contribution of anti-psychotic agents to the above results.
Schizophrenia
and epilepsy: clinical and pathological
studies
J.R. Stevens*, C.J. Bruton, C.D. Firth Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeth’s Hospital, Washington, DC 20032, USA.
The relationship between epilepsy, particularly temporal lobe epilepsy, and schizophrenia has long been of interest to investigators of both illnesses. With the goal of delineating anatomic sites of neuropathology and pertinent clinical data in individuals with epilepsy and a schizophrenia-like illness, clinical histories, EEG and brain pathology were examined for 13 individuals with a diagnosis of epilepsy plus schizophrenia during life compared with 37 individuals with a diagnosis of epilepsy but no psychosis. Patients diagnosed with epilepsy plus schizophrenia were all hospitalized and died at the Runwell Hospital, Essex, U.K., and were selected following review of the clinical records from a total of 651 patients with epilepsy, excluding material from patients with other psychoses, brain tumor, hemorrhage, Alzheimer’s disease, Huntington’s chorea, or postleukotomy seizures. Mean age at death of the 13 patients diagnosed with both epilepsy and schizophrenia was 67.5 years. Brain specimens from non-psychotic patients with epilepsy were from two sources: 1) individuals
374 whose epilepsy was so severe or whose family resources were so limited as to require the patient’s full time residency in an epileptic colony (n = 21; mean age at death 61.5 years); 2) individuals with epilepsy who were living and, in most cases, working in the community prior to death (n = 16, mean age 45.6 years). All brains were examined at the Runwell Hospital neuropathology laboratory where they were weighed, photographed and preserved in 10% formalin. Standard blocks and sections were prepared for histopathologic examination. Mean ages of onset of epilepsy differed between the three groups; community patients 23 years; schizophrenics 15.7 years; epileptic colony 6 years, but with a very wide variation for all three groups. Two schizophrenic patients developed the psychosis before the epilepsy; one coincident with epilepsy. Among the 10 others, onset of the chronic schizophrenia-like illness occurred 3 - 38 years after onset of epilepsy (mean 21.8 years). Differences in types of epilepsy, personal and family history and pathologic findings among the three groups are compared to delineate clinical and neuropathologic factors significantly related to development of a schizophrenia-like psychosis in individuals with epilepsy. Research supported by the Stanley Foundation, U.S.A.
Borna disease virus and schizophrenia: R.W. Waltrip*,
R.W. Buchanan,
K.M. Carbone,
Preliminary
results
A. Breier, 0. Narayan, W.T. Carpenter
Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD 21228, USA.
Viral and immunological etiological hypotheses in schizophrenia are considered attractive because they can account for a diverse range of manifestations. However, studies have yielded few specific findings, and no consistent associations with common CNS viruses. Preliminary data from an ongoing study of antibodies to Borna Disease Virus (BDV) antigen in patients referred to a research clinic with a presumptive diagnosis of schizophrenia indicates that: (1) nine of 49 patients (18%) have IgG antibodies to BDV and (2) the antibodies from the patients recognize the same intracellular antigen in a BDV-infected cell line as antibodies from a rabbit with BDV encephalitis. BDV is a highly neurotropic agent whose only known natural hosts are horses and sheep in central Europe. BDV is studied as a laboratory model of CNS-virus induced behavioral abnormalities. It has an extremely wide experimental host range, including avians, rodents, and primates. The manifestations of the disease depend upon the strain of virus and the species of host, ranging from asymptomatic infection through chronic forms to an acute fatal meningoencephalitis. BDV is exclusively neurotropic in adult animals, has a predilection for limbic structures and produces an immunopathological disease. Recent studies for the presence of antibodies to BDV in humans in the U.S. and Europe with psychiatric disease and neurological disease have been stimulated by observations of the behavioral abnormalities in animals. A seroprevalence ranging from 2 to 13% of antibodies to BDV in different populations has been observed. We are approaching this issue by screening schizophrenic patients for antibodies to BDV and characterization of seropositive individuals. A discussion of the biology of BDV with a focus on recent findings in animal models and observations in human populations will be presented. Screening and confirmation methods using single and double indirect immunofluorescence as well as clinical and MRI imaging findings contrasting seropositive and seronegative patients in our studies will be presented.