Handbook of Neurochem. and Molec. Neurobiology - Schizophrenia - D. Javitt, et al., (Springer, 2009) WW.pdf

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Handbook of Neurochemistry and Molecular Neurobiology
Schizophrenia
Abel Lajtha (Ed.)
Handbook of
Neurochemistry and
Molecular Neurobiology
Schizophrenia
Volume Editors: Daniel C. Javitt and Joshua T. Kantrowitz
With 62 Figures and 46 Tables
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Editor
Abel Lajtha
Director
Center for Neurochemistry
Nathan S. Kline Institute for Psychiatric Research
140 Old Orangeburg Road
Orangeburg
New York, 10962
USA
Volume Editors
Daniel Javitt
Director, Program in Cognitive Neuroscience and
Schizophrenia
Nathan Kline Institute for Psychiatric Research
140 Old Orangeburg Road
Orangeburg
New York, 10962
USA
javitt@nki.rfmh.org
Joshua Kantrowitz
Nathan Kline Institute for Psychiatric Research
140 Old Orangeburg Road
Orangeburg
New York, 10962
USA
JKantrowitz@nki.rfmh.org
Library of Congress Control Number: 2006922553
ISBN: 978 ‐ 0 ‐ 387 ‐ 30365 ‐ 9
Additionally, the whole set will be available upon completion under ISBN: 978 ‐ 0 ‐ 387 ‐ 35443 ‐ 9
The electronic version of the whole set will be available under ISBN: 978 ‐ 0 ‐ 387 ‐ 30426 ‐ 7
The print and electronic bundle of the whole set will be available under ISBN: 978 ‐ 0 ‐ 387 ‐ 35478 ‐ 1
2009 Springer Science þ Business Media, LLC.
All rights reserved. This work may not be translated or copied in whole or in part without the written permission
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Printed on acid ‐ free paper
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Preface
The field of Neuroscience has, in the past decades, undergone an explosive growth and developed very
impressive approaches and very exciting and important findings on how the mechanisms in the nervous
system operate. In spite of these really significant advances, our efforts to understand, cure, and prevent
pathological changes have not been so successful. Mental disease to many means life-long incapacity, which
affects more people in its various forms and for a longer time than any other disease, and represents a major
financial burden on society, but its elimination remains unfulfilled. We still do not know whether
schizophrenia or any other mental disease is a possible manifestation of separate pathologies and if so,
what the biological similarities and differences between our diagnostic classes are. Of course even temporary
help that diminishes the manifestations of the illness, and diminishes the associated suffering of the specific
hospital populations, is of great importance and represents a crucial contribution. Clearly mental illness
affects not only the patients; it is a burden on families and on the whole society; it diminishes contributions
to society, the productive life and the happiness of the patients suffering from it.
In spite of this, there is a dramatic decrease in hospital population and in incapacitated patients,
showing that the field is advancing, and that old dogmas have been replaced by new ones, and we have
new hope. The field is constantly advancing: we possess better drugs, better understanding, and more
knowledge. Certainly, knowledge of the basic mechanisms that ultimately modulate behavior and its
changes, determine pathology, the structure of receptors, of the cells, the interaction of the components,
connections, plasticity, measuring physiological processes, is constantly advancing. With such increasing
knowledge comes our recognition of the complexities of neural processes – especially the ones that govern
behavior, and the ones that are responsible for malfunction. The complexity requires a multifaceted
research approach; it therefore works best if a number of subdivisions collaborate. The use of structural,
imaging, genetic, electrophysiological, pharmacological, and biological expertise, looking at interaction of
specific proteins and of structural elements is needed. The knowledge of susceptibility and much more is
now essential for a better understanding of these complex mechanisms, which, however, seem more and
more within reach. Clearly a better understanding will represent a major accomplishment for mankind,
with immense medical, cultural, human and economic importance.
This volume also shows that it is impossible to predict from where the next advances in schizophrenia
research will come. For example, in the early 1980s, I led a study looking at the effects of a series of amino
acids and amino acid derivatives on the behavioral effects of phencyclidine. Of the amino acids we tested,
only glycine and the glycine derivative glycyldodecylamide were found to have a significant behavioral
effect. At the time, NMDA receptors had not yet been described, nor the inhibitory effects of phencyclidine
on NMDA function. Certainly, the glycine site of the NMDA complex had not been described. It would have
been impossible to predict that about a decade later these findings would contribute to the development of
new classes of medication, such as glycine transport inhibitors, that are currently in clinical trials for
schizophrenia, or that much of the work underlying this development would be conducted at my own
institution. Hopefully, the clues that will lead to further advances in the understanding and treatment of
schizophrenia can be found in this volume.
The multifaceted approach needed for further research development is clearly accomplished in the
present volume thanks to its Editors – multidisciplinary researchers themselves. Each chapter in itself – even
though it represents an approach to specific aspects of schizophrenia distinctly different from the others –
still reflects this need for a complex approach. Each deals with molecular mechanisms, but of different
genes, expressing different proteins; each deals with structures, which derive larger structures such as the
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vi
Preface
cortex, to smaller structures such as specific receptors, from the relevance of models to the relevance of
family studies. They show the wealth of available approaches and the exciting results of this work. These fine
reviews should help the field by pointing out not only what has been found and established, but also what
else needs to be found. It shows the successes of collaborative studies and the possibilities of such
collaborative studies in the future. Mental disease is not only a major burden, it also represents as shown
in these chapters, a major possibility to approach and understand behavior, its factors and mechanisms. By
pointing out current knowledge, it also indicates the promise of further understanding and improvement of
available therapies for patients. A great deal has been accomplished – a great deal is yet to be accomplished.
This volume shows us not only the accomplishments of the present, but also a hope for our future.
Abel Lajtha
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