Postmortem investigations of the pathophysiology of schizophrenia: the role of susceptibility genes

Despite robust evidence for the heritability of schizophrenia, postmortem studies have not traditionally linked cellular and molecular neuropathology with underlying genetic mechanisms in this disorder. The completion of the first draft of the Human Genome Project and the use of novel strategies in...

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Bibliographic Details
Published in:Journal of psychiatry & neuroscience 2004-07, Vol.29 (4), p.287-293
Main Authors: PERLMAN, William R, WEICKERT, Cynthia Shannon, AKIL, Mayada, KLEINMAN, Joel E
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Biological and medical sciences
Catechol O-Methyltransferase - genetics
Causes
Corpus Striatum - metabolism
Corpus Striatum - physiopathology
CRSN Symposium
Dopamine
Dopamine - metabolism
Fundamental and applied biological sciences. Psychology
gamma-Aminobutyric Acid - metabolism
Genetic Predisposition to Disease
Genetics
Glutamate
Humans
Medical sciences
Pathology
Prefrontal Cortex - metabolism
Prefrontal Cortex - physiopathology
Psychoanalysis
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Psychoses
RNA, Messenger - genetics
Schizophrenia
Schizophrenia - genetics
Schizophrenia - metabolism
Schizophrenia - physiopathology
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Summary:Despite robust evidence for the heritability of schizophrenia, postmortem studies have not traditionally linked cellular and molecular neuropathology with underlying genetic mechanisms in this disorder. The completion of the first draft of the Human Genome Project and the use of novel strategies in studying complex genetic disorders including schizophrenia have led to the identification of a growing list of schizophrenia susceptibility genes. In this review, we describe the strategy used to incorporate 2 potential schizophrenia susceptibility genes in the postmortem investigation of the pathophysiology of schizophrenia driven by 2 well-established hypotheses, the dopamine hypothesis and the neurodevelopmental hypothesis. The first gene codes for catechol-O-methyltransferase, an enzyme involved in catecholamine degradation, and the second gene codes for brain-derived neurotrophic factor, a growth factor implicated in cell survival, synaptogenesis and the development of cortical pyramidal neurons.
ISSN:1180-4882
1488-2434