About the Book
In 1990, the World Health Organization rated schizophrenia as one of the ten leading causes of disability which affects almost one percent of the world's population. Thus, almost 50 million people, the equivalent of a larger European nation, are afflicted by this disorder. The human suffering, family tragedies and financial burden represent a tremendous challenge for the scientific community. Emil Kraepelin and Eugene Bleuler, the founding fathers of the schizophrenia or dementia praecox concept, both postulated that this mental disorder originates in the brain - but as Kraepelin stated almost exactly 100 years ago "The causes of dementia praecox are at the present time still wrapped in impenetrable darkness". Although, since then ongoing, accelerating research efforts have resulted in the accumulation of almost fifty thousand scientific articles and hundreds of symposia on the subject, it has still not been possible to penetrate the "darkness" of the pathophysiological mechanisms for these disorders.
Even with today's advanced medical care, schizophrenic patients are deprived an objective diagnostic evaluation and the institution of therapeutic modalities with a strictly causal mechanism of action. Thus lifelong suffering continues, although the drug treatments instituted over the past 50 years have contributed to a reduction of some symptoms, of closed wards and compulsory treatment. Staffan was a somewhat reserved, but brilliant boy in his high school years. His Swedish essays were repeatedly read aloud by his language teacher as excellent examples for less talented students. Staffan was also a very witty person. One of his proverbs goes "There are three kinds of people, those who can count and those who cannot". This slightly bizarre joke might in retrospect represent a vague prodrome for his disorder that soon developed with grandiose ideas, delusional symptoms of poisoning and persecution and with auditory hallucinations of commentary type. When Staffan took his life at the age of 24, he had been offered all available treatments with, as he experienced, little help.
This type of patient history is heard repeatedly and reflects the situation for many patients with schizophrenia. According to all current diagnostic schemes schizophrenia is still an exclusively clinical diagnosis based upon the evaluation of reported and observed psychiatric symptoms. There is yet no accepted biological validation of the diagnosis. The challenge is to see schizophrenia not only as a health problem, but also a serious mishap of nature allowing us to explore and understand mind/body interactions, and higher mental functions. The hope for further progress relies upon development of a number of different basic and clinical neuroscience areas. Although infection theories have not been written off, schizophrenia is often viewed as a consequence of early trauma or defects in the development or maturation of the brain. Among several postulated causative factors, up to 70 per cent of the risk has been attributed to genetic mechanisms. Developments in molecular genetics, brain imaging and psychopharmacology represent important avenues for current research efforts.
Table of Contents:
Introduction. List of participants. Schizophrenia, the fundamental questions (N. C Andreasen). Familial and genetic mechanisms in schizophrenia (E. Fuller Torrey and R.H. Yolken). Schizophrenia as the price that Homo sapiens pays for language: a resolution of the central paradox in the origin of the species (T.J. Crow). Early and late environmental risk factors for Schizophrenia (C. McDonald, R.M. Murray). Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in Schizophrenia (W. E Bunney, B.G. Bunney). Lessons from childhood-onset Schizophrenia (J. Rapoport). Neurobiological findings in early phase Schizophrenia (D. Copolov, D. Velakoulis, P. McGorry, C. Mallard, A. Yung, S. Rees, G. Jackson, A. Rehn, W. Brewer and C. Pantelis). Obstetric complications and congenital malformation in Schizophrenia (T.F. McNeil, E. Cantor-Graae and B. Ismail). Molecular Genetic Studies of Schizophrenia (M. Owen). Critical overview of current approaches to genetic mechanisms in Schizophrenia research (L.E. DeLisi). Endogenous retroviruses and Schizophrenia (R. H. Yolken, H. Karlsson, F. Yee, N.L. Johnston-Wilson, E.F. Torrey). Stereological studies of the schizophrenic brain (J.J. Thune, B. Pakkenberg). Basal forebrain in the context of Schizophrenia (L. Heimer). Basal ganglia and cerebellar loops: motor and cognitive circuits (F.A. Middleton, P.L. Strick). Emerging principles of altered neural circuitry in Schizophrenia (F.M. Benes). GABAergic local circuit neurons and prefrontal cortical dysfunction in Schizophrenia (D.A. Lewis). Possible implications of the dopamine D3 receptor in Schizophrenia and in antipsychotic drug actions (J.-C. Schwartz, J. Diaz, C. Pilon, P. Sokoloff). Glutamate receptor expression in schizophrenic brain (J.H. Meador-Woodruff, D.J. Healy). D1 receptors in prefrontal cells and circuits (P.S. Goldman-Rakic, E.C. Muly, III, G.V. Williams). Serotonin model of Schizophrenia: emerging role of glutamate mechanisms (G.K. Aghajanian, G.J. Marek). The DARPP-32 knockout mouse (A.A. Fienberg, P. Greengard). Dysfunctional brain dopamine systems induced by psychotomimetic NMDA receptor antagonists and the effects of antipsychotic drugs (T.H. Svensson). Gating of information flow within the limbic system and the pathophysiology of Schizophrenia (A. A. Grace). Network interactions in Schizophrenia - therapeutic implications (A. Carlsson, N. Waters, S. Waters, M.L. Carlsson). Eye movements and the search for the essence of Schizophrenia (P.S. Holzman). Explaining the symptons of schizophrenia: Abnormalities in the awareness of action (C.D. Frith, S.-J. Blakemore, D.M. Wolpert). The limbic cortex in Schizophrenia: focus on the anterior cingulate (C.A. Tamminga, M. Vogel, X.-M. Gao, A.C. Lahti, H.H. Holcomb). The role of endogenous sensitization in the pathophysiology of Schizophrenia: implications from recent brain imaging studies (M. Laruelle). Development of novel antipsychotic drugs (J. Tallman). Schizophrenia and the mechanisms of conscious integration (G. Tononi, G.M. Edelman). Schizophrenia: Pathophysiological mechanisms - a synthesis (L. Terenius).
