title: Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies.
abstract: Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses.
authors.affiliation: Harvard Medical School Department of Psychiatry at the Massachusetts Mental Health Center, Boston, MA, USA. sfarone@hms.harvard.edu
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
authors.forename: David
authors.initials: D
authors.lastname: Kennedy
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.forename: Verne S
authors.initials: VS
authors.lastname: Caviness
authors.forename: Jill
authors.initials: J
authors.lastname: Goldstein
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D001931:Brain Mapping; D016022:Case-Control Studies; D005163:Factor Analysis, Statistical; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010641:Phenotype; D012372:ROC Curve; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*