Viruses, Immunity, and Mental Disorders

468 Pages·1987·14.98 MB·English

by  D. Carleton Gajdusek (auth.)

Viruses,
Immunity, and
Mental Disorders
Viruses,
Immunity, and
MentalDisorders
Edited by
Edouard Kurstak
Faculty 0/ Medicine
University 0/ Montreal
Montreal, Quebec, Canada
Z. J. Li powski
Department 0/ Psychiatry
University 0/ Toronto
Toronto, Ontario, Canada
and
P. V. Morozov
World Health Organization
Geneva, Switzerland
Currently, Academy 0/ Medical Sciences 0/ the USSR
Moscow, USSR
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
Viruses, immunity, and mental disorders.
Based mostly on the First World Conference on Viral Diseases, Immunity, and Men
tal Health held in Montreal, Canada in Nov. 1984, and sponsored by the International
Comparative Virology Organization and the World Health Organization.
Includes bibliographies and index.
I. Mental illness - Etiology - Congresses. 2. Virus diseases - Psychological aspects
Congresses. 3. Mental illness-Immunological aspects-Congresses. 4. Psychological
manifestations of general diseases-Congresses. I. Kurstak, Edouard. 11. Lipowski, Z.
J. (Zbigniew Jerzy) 111. Morozov, P. V. IV. World Conference on Viral Diseases, Im
munity, and Mental Health (1st: 1984: Montn:al, Quebec) V. International Compara
tive Virology Organization. VI. World Health Organization. [DNLM: 1. Mental Dis
orders - etiology - congresses. 2. Mental Disorders - immunology - congresses. 3.
Virus Diseases - complication - congresses. 4. Viruses - pathogenicity - congresses.
WM 100 V821 1984]
RC455.4.B5V57 1987 616.89'071 87-2478
ISBN 978-1-4612-9007-0 ISBN 978-1-4613-1799-9 (eBook)
DOI 10.1007/978-1-4613-1799-9
© 1987 Springer Science+Business Media New York
Originally published by Plenum Publishing Corporation in 1987
Softcover reprint of the hardcover 1 st edition 1987
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Preface
In spite of progress in biomedical research, we know little about the causes, prevention,
and treatment of the numerous mental and neurological disorders that afflict up to 15%
of all individuals.
In the last decade, great advances have been made in the physiopathology of mental
and neurological disorders, leading to at least a partial control of Parkinson's disease,
epilepsy, certain psychoses, and anxiety syndromes. Despite the fact that an underlying
specific neurotransmitter deficiency has been demonstrated in Alzheimer's and Parkinson's
diseases, the immune dysfunction and viral hypotheses continue to be attractive for
investigators dealing with these degenerative diseases of the aging brain, which afflict
10% of senior citizens. A retrospective epidemiologic study suggests that the encephalitis
lethargica and parkinsonism were almost certainly caused by the 1918 influenza virus
pandemics. It must be stressed that the etiopathogenesis of many mental disorders is not
known, and this ignorance has led to several untenable neurophysiological and biochemical
hypotheses.
Epidemiologic investigations show a high prevalence of functional psychoses and
organic mental disorders. Although many of them are conceptualized as biopsychosocial
disorders, recent data indicate that the biological component appears more and more as
a major etiologic factor. Among the various biological hypotheses, the viral and im
munologic concept has become a significant one. In view of recent discoveries in virology
and immunity, it becomes clear that viral and immunologic hypotheses should be inves
tigated more systematically concerning the mechanisms of numerous mental and neu
rological disorders.
Several laboratories are already engaged in research on multiple sclerosis and its
relationship to a combination of conventional viruses such as measles and Epstein-Barr
viruses and an abnormal immune response in affected patients. In Africa, where almost
all children are infected at a young age with measles or Epstein-Barr viruses and become
immune to these viruses, multiple sclerosis is very rare or even unknown. It is known
that chronic Epstein-Barr virus infection and resulting infectious mononucleosis are as
sociated with cerebral dysfunction and depression and that residual mental disorders after
herpes simplex virus infections are not to be underestimated.
Neuropsychiatric complications of acquired immune deficiency syndrome (AIDS),
caused by a retrovirus infection, with illness progression are very serious, resulting in
psychotic behavior with paranoid features, a severe anxiety state, hallucinations, and
depression. The physicians working with AIDS patients know that behavioral disturbances
are manifestations of an organic mental syndrome.
However, most exciting are the latest data from research on unconventional path-
v
vi PREFACE
ogenic viruses in the transmissible dementias and other brain disorders or on unconven
tional infectious agents, named prion rods, with novel molecular structure and properties
causing degenerative neurological disorders in animals. These rod structures have been
found in the brains of patients with Creutzfeldt-Jakob disease and kuru and not in normal
control brains or brains of patients with other neurodegenerative diseases. The existence
of two forms of cerebral amyloidoses, transmissible and nontransmissible, is postulated.
The transmissible form is caused by the unconventional scrapie, kuru, and Creutz
feldt-Jakob viruses, which are associated with the formation of an amyloid subunit protein.
The nontransmissible form and its amyloid subunit protein are deposited in amyloid or
neuritic plaques, and perivascularly in lesions of congophilic angiopathy. The second
form is most commonly seen in lesions of Alzheimer's disease, senile dementia of
Alzheimer's type, Guamanian parkinsonism-dementia, and Pick's disease, and in the
brain of Down's syndrome patients. We already know the host gene encoding the precursor
protein for the amyloid of the slow virus infections in scrapie, kuru, and Creutzfeldt-Jakob
diseases. The precursor of the noninfectious amyloidoses of brain, like Alzheimer's
disease, Down's syndrome, and senility, remains unknown.
In the case of schizophrenia, an elegant hypothesis is that the disease is related to
the replication of a retrovirus gene that would exist as a provirus within the human genome
and could be passed from one generation to the next. Considering such a possibility, the
disease occurs either as a result of inheritance from an affected or predisposed parent or
as a result of an integration or transposition event occurring early in ontogeny. A very
interesting case is the demonstration of antibodies to bornavirus in patients with affective
disorders. This neurotropic virus affects the brain limbic area and can produce a behavioral
syndrome in some animal species that is characterized by aggressive and passive phases.
Psychological and neurological changes in animals were also observed as a result of
persistent coronavirus infection of the central nervous system resulting in demyelinating
disease.
The association of immune system abnormalities and dysfunction with the etiology
of mental disorders is another area of present active investigation in several laboratories.
Numerous reports describe such immune abnormalities among patients with major psy
chiatric disorders, particularly schizophrenia and depression. Decreased immunoglobulin
concentrations, decreased macrophagefunctioning, decreased natural killer cell activity,
increased suppressor-cell percentages, and increased B-cell percentages were reported in
schizophrenic patients. In 20% of chronic hospitalized psychiatric patients antinuclear
antibodies are found at a high level. Antibodies to brain tissue in sera from schizophrenic
patients were also reported, as well as evidence of lymphocyte abnormality in schizo
phrenia. Chronic neuropsychiatric disorders such as schizophrenia and Huntington's dis
ease may be characterized by alterations in T-Iymphocyte number, morphology, and
function. Similar alterations accompany cytomegalovirus and Epstein-Barr virus infec
tions, which could be implicated in the pathogenesis of schizophrenia. Cytomegalovirus
antigens were found in the brains of schizophrenic patients. It also was demonstrated that
responses to T-cell and T-dependent B-cell mitogens, as well as the absolute number of
lymphocytes and T and B cells, were significantly lower in drug-free hospitalized patients
with major depressive disorders than in apparently healthy matched controls, which
suggests that depression is associated with altered immune function. However, the changes
in lymphocyte function in major depressive disorders may be related to the hyperadren-
PREFACE vii
alism associated with depression. Many depressed patients have increased levels of cor
tisol, an immunosuppressive hormone, in circulation. Other interesting findings are the
defect in interferon production in leukocyte cultures of schizophrenic patients and pre
liminary observations on clinical improvement of schizophrenic patients treated with
purified human leukocyte interferon.
The importance of recent research data on the role of biological factors in mental
and neuropsychiatric disorders, particularly implicating the viral and immunologic hy
potheses, justified the organization in Montreal, Canada, of the First World Conference
on Viral Diseases, Immunity, and Mental Health, and the publication of this volume.
No comparable treatise on this subject is available to give in a single volume detailed
information on new research developments by virologists, immunologists, neurologists,
geneticists, and psychiatrists.
This volume is divided into five major parts: I-Viruses and Organic Mental Dis
orders; II-Viruses and Functional Mental Disorders; III-In Vivo and In Vitro Models
for Viral Etiology of Neuropsychiatric Diseases; IV-Immunity, Interferon, and Psy
chiatric Disorders; and V-Stress and Depression and Susceptibility to Virallnfection, and
Psychiatric Aspects.
All chapters were prepared by well-known experts in their fields and include the
latest fundamental and clinical research data, overviews, and hypotheses.
Sincere thanks are addressed to each contributor for a thoughtful and well-docu
mented treatment of his subject. The material included in this volume, the personal
interpretations and conclusions of the authors, provides a large body of information and
brings into sharp focus both current findings and the new directions of multidisciplinary
research needed in biological psychiatry.
It is our conviction that this treatise will be useful to all psychiatrists, as well as
virologists, immunologists, neurologists, and geneticists, interested in the newest devel
opments in biological psychiatry.
I wish to express my thanks and gratitude to the Honorable Jake Epp, Minister of
National Health and Welfare of Canada; to Dr. Pierre Bois, President of the Medical
Research Council of Canada; to Dr. Yvon Gauthier, Dean of the Faculty of Medicine of
the University of Montreal; to Dr. Serge Carriere, President of the Fonds de Recherche
en Sante du Quebec; and to Dr. Charles Merieux, President of the Merieux Foundation,
France, for the financial assistance provided to publish this monograph and to organize
the conference, which was sponsored by the International Comparative Virology Organ
ization and the World Health Organization.
I am particularly grateful to Professor Z. J. Lipowski and Dr. P. V. Morozov, who
cochaired the conference with me and worked efficiently as coeditors of this volume,
and to Professors Lydia and Vincent Adamkiewicz for reference help.
The editors' thanks and gratitude are also addressed to the staff of Plenum Publishing
Corporation for their part in the production of Viruses, Immunity, and Mental Disorders.
Edouard Kurstak
Director
International Comparative
Virology Organization
Montreal, Canada
Contents
Introduction ........................................................ xiii
I. Viruses and Organic Mental Disorders
1. The Transmissible Dementias and Other Brain Disorders Caused by
Unconventional Viruses: Relationship of Transmissible to Nontransmissible
Amyloidosis of the Brain .......................................... 3
D. Carleton Gajdusek
2. Prion Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Stanley B. Prusiner, Ronald A. Barry, Michael P. McKinley,
Carolyn G. Bellinger, Rudolf K. Meyer, Stephen J. DeArmond,
and David T. Kingsbury
3. Transmission Studies of Psychiatric and Neurological Disease: Some
Reflections on the Nature of the Agent in Transmissible Dementia and the
Pathogenesis of Neurodegenerative Disease ........................... 33
R. M. Ridley, H. F. Baker, and T. J. Crow
4. The Viral Hypothesis in Parkinson's Disease and in Alzheimer's Disease: A
Critique ........................................................ 47
Teresita S. Elizan and Jordi Casals
5. Organic Dementia of the Alzheimer Type: Possible Role of Reactivated
Herpes Simplex Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Melvyn J. Ball
6. Residual Mental Disorders after Herpesvirus Infections . . . . . . . . . . . . . . . . . . 65
Richard Greenwood
7. Infectious Mononucleosis and Psychiatric Disorders. . . . . . . . . . . . . . . . . . . . . 81
Nelson Hendler
8. Psychiatric Aspects of AIDS: The Organic Mental Syndromes. . . . . . . . . . . . 95
Richard J. Loewenstein and David R. Rubinow
9. AIDS Retrovirus and Other Viruses in Brain and Hematopoietic Cells of
Patients in Early and Late Stages of the Acquired Immune Deficiency
Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109
Ferenc Gyorkey and Joseph L. Melnick
ix
x CONTENTS
II. Viruses and Functional Mental Disorders
10. Genes and Viruses in Schizophrenia: The RetroviruslTransposon
Hypothesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 125
Timothy J. Crow
11. Investigations on the Possible Role of Viruses Affecting the CNS in the
Etiology of Schizophrenia and Related Mental Disorders. . . . . . . . . . . . . . . .. 135
J. Rajcani, H. Librkova, J. Smerekova, V. Mucha, M. Kudelova,
J. Pogady, S. Breier, and I. Skodacek
12. Schizophrenia: An Epidemiologic, Immunologic, and Virological Approach 149
Carlo Lorenzo Cazzulio, Domenico Caputo, Laura Beliodi,
Cesare Maffei, Pasquale Ferrante, Fernanda Bergamini,
Maria P. Landini, and Michele La Placa
13. Paramyxoviruses in the Brain in Febrile Schizophrenia. . . . . . . . . . . . . . . . .. 157
Victor M. Vostrikov and Akim I. Oifa
14. Cytotoxic CSF from Neurological and Neuropsychiatric Patients: Is the
Cytopathic Effect Caused by a Virus? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161
G. R. Taylor, G. I. Carter, and T. J. Crow
15. Antibody- and Cell-Mediated Immunity to Herpes Simplex and Epstein-Barr
Viruses in Psychotic Patients ....................................... 173
T. Gotlieb-Stematsky, S. Floru, D. Becker, E. Kritchman,
and S. Leventon-Kriss
16. Demonstration of Antibodies to Boma Disease Virus in Patients with
Affective Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 179
Jay D. Amsterdam, Andrew Winokur, William Dyson, Sibylle Herzog,
Francisco Gonzalez, Rudolf Rott, and Hilary Koprowski
III. In Vivo and in Vitro Models for Viral Etiology of Neuropsychiatric Diseases
17. Animal Models in Behavioral Neurovirology .......................... 189
Dennis McFarland and John Hotchin
18. In Vivo and in Vitro Models of Demyelinating Disease: Factors Influencing
the Disease Process Caused by Coronavirus Infection of Rats. . . . . . . . . . . .. 199
O. Sorensen, S. Beushausen, M. Coulter-Mackie, R. Adler,
and S. Dales
19. Importance of the Antibody Response in the Outcome of Virus-Induced
Diseases of the Central Nervous System: Antibody Modulation of
Coronavirus Encephalitis in a Mouse Model. . . . . . . . . . . . . . . . . . . . . . . . . .. 211
Pierre J. Talbot, Robert L. Knobler, and Michael J. Buchmeier
CONTENTS xi
20. The Herpes Simplex Virus Infection of the Rat Sensory Neuron. . . . . . . . . .. 221
Erik Lycke, Bo Svennerholm, Anders Vahlne,
and Richard J. Ziegler
21. In Vitro Cultivation of Nerve Cells as a Model for Studies on Nerve Cell-
Virus Interactions ................................................ 227
Richard J. Ziegler
22. Rabies Impainnent of Neural Functions by Neurophannacological and
Electrophysiological Criteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 235
Henri Tsiang, Rugimar Marcovistz, and Patrick Gourmelon
23. Paramyxovirus-Induced Changes of ~-Adrenergic Receptor Response and Its
Immunologic Modulation .......................................... 245
Klaus Koschel, P. Noel Barrett, Roland Metzner,
and Jutta Zinnheimer
24. Dopamine Receptors and Monoamine Oxidase as Virus Receptors:
Preliminary Tests of the Hypothesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 257
Edward G. Shaskan, John D. Shanley, Lars Oreland,
and Goran Wadell
IV. Immunity, Interferon, and Psychiatric Disorders
25. Immunologic Studies of Schizophrenic Patients 271
Lynn Eleanor DeLisi
26. Some Aspects of Immunologic Studies in Schizophrenia. . . . . . . . . . . . . . . .. 285
G. I. Kolyaskina, T. P. Sekirina, A. A. Zozulya, S. G. Kushner,
M. fa. Zuzulkovskaya, and L. I. Abramova
27. Humoral Immunity of Schizophrenic Patients of Siberia and the Far East . .. 295
O. A. Vasiljeva, T. P. Vetlugina, H. Libfkova, J. Rajcani,
G. V. Logvinovitch, V. fa. Semke, P. P. Balashov,
and A. A. Shmelyov
28. T-Lymphocyte Subsets and Schizophrenia. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 307
Charles A. Kaufmann, Lynn E. DeLisi, E. Fuller Torrey,
Susan E. Folstein, and William J. Smith
29. T Lymphocytes in Schizophrenics and Nonnals and the Effects of Varying
Antipsychotic Dosage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321
Rohan Ganguli, Bruce Rabin, Usha Raghu, and Richard S. Ulrich
30. Evidence of Lymphocyte Abnonnality in Schizophrenia. . . . . . . . . . . . . . . .. 327
Motoe Hirata-Hibi, Motow Oh, Kazuko Miyauchi,
and Takehiko Tachibana