VENTRICULAR ENLARGEMENT ASSOCIATED WITH LINKAGE MARKER FOR SCHIZOPHRENIA-RELATED DISORDERS IN ONE PEDIGREE

We previously obtained evidence indicating a genetic linkage marker fo r schizophrenia and related disorders (two-point lod score = 3.72, P = 0.01) on the short arm of chromosome 5(5p14.1-13.1) in one large pedi gree. Automated computer algorithms were used to edge the brain and me asure the volume of the ventricles, regional sulcal atrophy, and skull size and shape in the original nuclear family members, Of the 11 subj ects who underwent computed tomography, six (three schizophrenic, two with schizotypal personality disorder, and one unaffected) carried the marker allele that cc-segregated with schizophrenia-related disorders , while five (all unaffected) did not. The family members with the mar ker allele linked to schizophrenia-related disorders (n = 6) had signi ficantly (P < 0.05) larger ventricle-brain ratios (VBRs) and more fron to-parietal atrophy (controlling for age) than the family members lack ing the schizophrenia-related marker allele (n = 5). The three individ uals with the largest VBRs all carried the marker, although they recei ved diagnoses of no schizophrenia-related disorder, schizotypal person ality disorder, and schizophrenia. Regional cortical values indicative of cerebrospinal fluid content were higher in the frontal and parieta l regions of family members carrying the marker, The hypothesis that g enetic linkage is associated with structural brain pathology is diffic ult to test because of all the potential compounding factors, Our find ings suggest the possibility that; in this family, relatively enlarged VER and fronto-parietal atrophy, as determined by computed tomography , may be associated with a schizophrenia-related gene and present susc eptibility to schizophrenia-related disorders. In addition to a replic ation of these findings in other similarly linked families yet to be i dentified, further studies using higher resolution structural and func tional neuroimaging techniques will be required.