Cortical mapping of genotype-phenotype relationships in schizophrenia.
Although schizophrenia is highly heritable, the search for susceptibility genes has been challenging. The "endophenotype" approach is an alternative method for measuring phenotypic variation that may make it easier to identify susceptibility genes in the context of complexly inherited traits. Neuroimaging methods in particular offer a powerful way to bridge the neurobiology of genes and behavior. Such investigations may be further empowered by complementary strategies involving chromosomal abnormalities associated with schizophrenia, which can help to localize causative genes and better understand the genetic complexity of the illness. Here, we illustrate our use of these convergent approaches, with a focus on neuroimaging studies using novel computational brain mapping algorithms, to investigate genetic influences on brain structure in the development of psychosis. These studies provide compelling evidence that specific genetic loci suspected to predispose to schizophrenia may affect quantitative variation in neural indicators underlying the neurobehavioral phenotype, and illustrate how genetic-neuroimaging paradigms can improve our understanding of the pathogenesis of this highly disabling mental illness.
Bearden
Carrie E
CE
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90095, USA. cbearden@mednet.ucla.edu
van Erp
Theo G M
TG
Thompson
Paul M
PM
Toga
Arthur W
AW
Cannon
Tyrone D
TD
D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology