title: Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia.
abstract: Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures.
authors.affiliation: Harvard Medical School and Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02129, USA. jroffman@partners.org
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Roffman
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weiss
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D012565:Schizophrenic Psychology