Clinical features of schizophrenia and linkage to chromosomes 5q, 6p, 8p, and 10p in the Irish study of high-density schizophrenia families

Objective: Schizophrenia is clinically heterogeneous. Recent linkage studie s suggest that multiple genes are important in the etiology of schizophreni a. The authors examined the hypothesis of whether the clinical variability in schizophrenia is due to genetic heterogeneity. Method: Using data from t he Irish Study of High-Density Schizophrenia Families (N = 265 pedigrees; N = 1,408 individuals), the authors attempted to predict, from major symptom s and signs of psychosis, evidence for linkage within families for schizoph renia-related disorders to chromosomal regions 5q21-5q31, 6p24-6p22, 8p22-8 p21, and 10p15-10p11. Results: No substantial evidence was found for associ ations between clinical features of schizophrenia and linkage to chromosome s 50, 6p, or 10p. However, affected individuals from families with evidence for linkage to 8p had significantly more affective deterioration, poorer o utcome, more thought disorder. and fewer depressive symptoms than affected individuals from the other families in the study. Conclusions: These result s raise the possibility that the putative susceptibility gene for schizophr enia localized in the 8p22-8p21 region may predispose individuals to the co re dementia-praecox syndrome described by Kraepelin more than 100 years ago .