Elucidating continuities and discontinuities between schizotypy and schizophrenia in the nervous system

Genetic epidemiological studies indicate that schizophrenia is a complexly inherited disorder, whereby multiple genes, additively and in interaction with environmental factors. contribute to increasing risk for phenotypic expression. Linkage studies have identified a number of chromosomal regions as likely to harbor susceptibility genes for schizophrenia, but the linked regions span relatively large chromosomal segments in each case. These efforts have been hindered in part by a lack of means to detect nonpenetrant carriers of predisposing genes and in part by uncertainties concerning the nature of the nongenetic factors involved and their mechanisms of action in relation to genetic factors. Our strategy has focused on elucidating changes in central nervous system structure, physiology, and function that mark an inherited genotype for schizophrenia and on identifying specific environmental and etiological contributors and their modes of action in relation to genetic factors. The research reviewed in this paper, making use of family and twin designs, suggests that certain neural system deficits in schizophrenia (e.g., prefrontal cortex, working memory) are reflective of an inherited diathesis to the disorder, while others (e.g., temporal cortex, episodic memory) result from the interacting influences of genetic factors and particular types of biologically disruptive environmental events (e.g., fetal hypoxia), These findings help to reveal continuities and discontinuities in the neural disturbances characteristic of the schizophrenia genotype and phenotype and encourage the use of quantitative neural trait measures in the search for schizophrenia susceptibility genes. (C) 2002 Elsevier Science B.V. All rights reserved.