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Schizophrenia: Pathophysiological Mechanisms

(1998, NS 111)
October 1-3, 1998
Nobel Forum, Karolinska Institutet, Stockholm, Sweden
Organizers: Professors Lars Terenius, Lars Farde, Göran Sedvall and Torgny Svensson, Karolinska Institutet.

The symposium drew about 100 people, of whom 37 were lecturers and two provided discussion presentations by previous notification. The symposium stressed that schizophrenia is very much a disease that disrupts the ability to think and may be the price that humans as a species must pay for their ability to use language. Its etiology is extremely unclear. Although infection theories have not been written off, the disease is often viewed as a consequence of defects in the development or maturity of the brain. It has been demonstrated that the disease has a genetic component. If one of two identical twins contracts it, the other runs a 50 percent risk of doing so.

Schizophrenic symptoms are relieved by drugs that block the receptors for the signal substance dopamine. These drugs take effect slowly, however, and today other signal substances are the focus of research, for example glutamate, serotonin and neuropeptides.

Research on the causes of schizophrenia can also be viewed in a broader perspective, since the disease affects the most unique qualities of the human species: its capacity for awareness, thinking and knowledge.

The symposium contributions were published both as a special issue of Brain Research Reviews and as a monograph (Elsevier) during the summer of 1999.


Programme  
October 1  
18.50 Welcome address
Göran Sedvall
  Ethiology
Chair: Daniel Weinberger
19.05-1920 Schizophrenia, the fundamental questions
Nancy C. Andreasen
19.25-19.40 Familial and genetic mechanisms in schizophrenia
E. Fuller Torrey
19.45-20.00 Schizophrenia as the price that Homo sapiens pay for language
Timothy Crow
20.05-20.20 Early and late environmental risk factors
Robin M. Murray
   
October 2 Brain development and schizophrenia
Chair: Robin Murray
8.45-9.00 Neuronal migration and schizophrenia
Pasko Rakic
9.05-9.20 Cytological abnormalities and brain development
William E. Bunney, Jr.
9.25-9.40 The brain and childhool schizophrenia
Judith Rapaport
9.45-10.00 Neurobiological findings in prodormal and early phase schizophrenia
David L. Copolov
10.05-10.20 Obstetric complications and congenital malformation in schizophrenia
Thomas McNeil
  Molecular genetic mechanisms and schizophrenia
Chair: Lars Farde
13.30-13.45 Thalamus and other brain regions
Bente Pakkenberg
13.50-14.05 Basal ganglia
Ann M. Graybiel
14.10-14.25 Ventral Forebrain
Lennart Heimer
14.30-14.45 Organization of basal ganglia output
Peter L. Strick
14.50-15.05 Emerging Principles of Altered Neural Circuitry in Schizophrenia
Francine M. Benes
15.10-15.25 Interneuron circuitry
David A. Lewis
15.30-15.45 Coffee break
  Neurotransmitter systems I
Chair: Torgny Svensson
15.50-16.05 Dopamine receptors and schizophrenia
Jean-Charles Schwartz
16.10-16.25 Dopamine and glutamate receptor mRNA expression in schizophrenia
James H. Meador Woordruff
16.30-16.45 Receptor specificity in prefrontal cortical circuitry and function
Patricia Goldman-Rakic
 
October 3 Neurotransmitter systems II
Chair: William E. Bunney, Jr.
8.25-8.40 Central serotonergic systems and schizophrenia
George Aghajanian
8.45-9.00 Beyond the dopamine receptor
Paul Greengard
9.05-9.20 Dysfunctional brain dopamine systems induced by psychotomimetic NMDA receptor antagonists
Torgny Svensson
9.25-9.40 Gating of information flow through limbic and thalamocortical systems and the pathophysiology of schizophrenia
Anthony A. Grace
9.45-10.00 The role of intrinsic prefrontal neurons in intracortical and dopaminergic deficits
Daniel R. Weinberger
10.05-10.20 Behavioural and biochemical effects of NMDA-receptor antagonists: Network interactions
Arvid Carlsson
10.25-10.30 Commentary
Frits-Axel Wiesel
10.30-10.50 Coffee break
  Brain imaging and cognitive functions
Chair: Nancy Andreasen
10.50-11.05 Smooth pursuit eye movements in schizophrenia
Philip S. Holzman
11.10-11-25 The cognitive neurophysiology of schizophrenia
Christopher Frith
11.30-11.45 Dynamic functional mapping of brain activity states related to drug action: Focus on the anterior cingulate cortex
Carol A. Tamminga
11.50-12.05 PET imaging of dopamine receptors in schizophrenia
Lars Farde
12.10-12.25 Increased amphetamine-induced dopamine release in schizophrenia. Evidence for a hyperdopaminergic state
Marc Laruelle
12.30-12.35 Commentary
Leif Lindström
  Integrative aspects
Chair: Arvid Carlsson
13.45-14.00 Principles in the development of novel antipsychotics
John Tallman
14.05-14.20 Reentrant interactions and neural correlates of consciousness in human subjects
Gerald M. Edelman
14.25-14.40 Functional clustering: Evaluating disorders of neural integration
Giulio Tononi
14.45-15.00 A synthesis
Lars Terenius

 

Participants
Dr. Ann M Graybiel
Dept. of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Cambridge, MA 02139, USA

Dr. Anthony A. Grace
Department of Neuroscience
University of Pittsburgh, PA 15260, USA

Dr. Arvid Carlsson
Department of Pharmacology
Göteborg University
Box 431
S-405 30 Göteborg, Sweden

Dr. Bente Pakkenberg
Neurological Research Laboratory
Kommunehospitalet
Copenhagen K, Denmark

Dr. Carol A. Tamminga
Maryland Psychiatric Research Center
University of Maryland at Baltimore
Baltimore, MD 21228, USA

Dr. Christopher Frith
Wellcome Department of Cognitive Neurology
Institute of Neurology
Queen Square
London WC1N 3BG, UK

Dr. Daniel R. Weinberger
Clinical Brain Disorders Branch, IRP, NIMH,
NIH Neuroscience Center at St. Elizabeth's Hospital
Washington, DC 20032, USA

Dr. David A. Lewis
Western Psychiatric Institute and Clinic
University of Pittsburgh
Pittsburgh, PA 15213-2593, USA

Dr. David L. Copolov
NH&MRC Schizophrenia Research Unit
Mental Health Research Institute of Victoria
Parkville, Australia

Dr. Francine M. Benes
Laboratory for Structural Neuroscience
McLean Hospital
Belmont, MA 02178, USA

Dr. Frits-Axel Wiesel
Department of Psychiatry
UlleÅker
750 17 Uppsala, Sweden

Dr. George Aghajanian
Department of Psychiatry
Yale University School of Medicine
New Haven, CT 06508, USA

Dr. Gerald M. Edelman
The Neurosciences Institute
Scripps Research Institute
Department of Neurobiology
La Jolla, CA 92037, USA

Dr. Giulio Tononi
The Neurosciences Institute
10640 John Jay Hopkins Drive
San Diego, CA 92121, USA

Dr. Göran Sedvall
Karolinska Institutet
Department of Clinical Neuroscience
Psychiatry Section
Karolinska Hospital
S-171 76 Stockholm, Sweden

Dr. James M. Meador-Woodruff
Mental Health Research Institute
University of Michigan
Ann Arbor, MI 48109-0720, USA

Dr. Jean-Charles Schwartz
Unite de Neurobiologie et Pharmacologie (U.
109) de I'INSERM
Centre Paul Broca
750 14 Paris, France

Dr. John Tallman
Neurogen Corporation
35 NE Industrial Road
CT 06405, USA

Dr. Judith Rapaport
Child Psychiatry Branch NIMH
9000 Rockville Pike Rd.
Bldg 10, Rm 2N640
Bethesda, MD 20892, USA

Dr. Kenneth S. Kendler
Department of Psychiatry and Human Genetics
Medical College of Virginia
Virginia Commonwealth University
Richmond, VA 23298, USA

Dr. Lars Farde
Karolinska Institutet
Department of Clinical Neuroscience
Psychiatry Section
Karolinska Hospital
S-171 76 Stockholm, Sweden

Dr. Lars Terenius
Karolinska Institutet
Department of Clinical Neuroscience
Experimental Alcohol and Drug Addiction Research
Karolinska Hospital
S-171 76 Stockholm, Sweden

Dr. Leif Lindström
Psykiatriska forskningsenheten
Centrallasarettet
S-721 89 Vasterås, Sweden

Dr. Lennart Heimer
Department of Anatomy
University of Virginia
Charlottesville, VA 22908, USA

Dr. Lynn E. DeLisi
Department of Psychiatry SUNY
Stony Brook, NY 11794, USA

Dr. Marc Laruelle
Department of Psychiatry
Yale University School of Medicine/VA Medical
Center
West Haven, CT 06516, USA

Dr. Michael Owen
Neuropsychiatric Genetics Unit
Tenovus Building
Heath Park
Cardiff CF4 4XN, UK

Dr. Nancy C. Andreasen
Department of Psychiatry
University of Iowa
Iowa City, IA 52242-1057, USA

Dr. Partricia Goldman-Rakic
Section of Neurobiology
Yale University School of Medicine
New Haven, CT 06510, USA

Dr. Pasco Rakic
Section of Neurobiology
Yale University School of Medicine
New Haven, CT 06510, USA

Dr. Paul Greengard
Laboratory of Molecular and Cellular
Neuroscience
Rockefeller University
New York, NY 10021, USA

Dr. Peter McGuffin
Department of Psychological Medicine,
University of Wales College of
Medicine, Heath Park
Cardiff, U.K

Dr. Peter L. Strick
Department of Physiology
SUNY Health Science Center at Syracuse
Syracuse, NY 13210, USA

Dr. Philip S. Holzman
Department of Psychology
Harvard University
Cambridge, MA 02138, USA

Dr. Robert H. Yolken
Stanley Laboratory for the Study of Schizophrenia and Bipolar Disease
Department of Pediatrics
Johns Hopkins University
Baltimore, MD 21205, USA

Dr. Robin M. Murray
Department of Psychological Medicine
Institute of Psychiatry
De Crespigny Park
London, SE5 8AF, UK

Dr. Steven E. Hyman
National Institute of Mental Health
Rockville, MD 20857, USA

Dr. Steven M. Paul
Lilly Research Laboratories
Eli Lilly and Company
Indianapolis, IN 46285, USA

Dr. Steven Pinker
Institution Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Cambridge, MA 02139, USA

Dr. Thomas McNeil
Dept of Community Medicine
University Hospital UMAS
S-205 02 Malmö, Sweden

Dr. Timothy Crow
University Department of Psychiatry
Warneford Hospital
Oxford OX3 7JX, UK

Dr. Torgny Svensson
Department of Physiology and Pharmacology
Karolinska Institutet
S-171 77 Stockholm, Sweden

Dr. William E. Bunney, Jr.
Department of Psychiatry
University of California at Irvine
Irvine, CA 92697, USA

 

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