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 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.
Perlman
William R
WR
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Md 20892-1384, USA.
Weickert
Cynthia Shannon
CS
Akil
Mayada
M
Kleinman
Joel E
JE
D002394:Catechol O-Methyltransferase / Q000235:genetics; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D002394:Catechol O-Methyltransferase; D004298:Dopamine