Twin study refining psychotic symptom dimensions as phenotypes for genetic research.

We investigated which psychotic symptom dimensions are likely to be most useful as phenotypes for genetic linkage and association studies. Two hundred twenty-four probandwise twin pairs (106 monozygotic,118 same-sex dizygotic), where probands had psychosis, were ascertained from the Maudsley Twin Register in London. Dimensions were defined as ordinal symptom scores using the OPCRIT checklist, based on previous factor analyses of this and other samples. To qualify as a potentially useful phenotype, dimensions had to show (a) a satisfactory polychoric model fit and significant within-pair correlation in MZ pairs concordant for DSM-III-R psychosis and (b) that they could not be better defined in terms of other combinations of relevant symptoms, single symptoms, or dichotomized dimension scores. Relationships between dimension scores in twin probands and risk of psychosis in co-twins were also investigated. None of the positive or negative dimensions satisfied the phenotypic criteria. The disorganized dimensions showed significant and substantial correlations which maximized for a narrow definition. Combined negative/disorganized dimensions also showed significant and substantial correlations, but did not have advantages over disorganized dimensions. None of the dimensions were significant predictors of psychosis risk in co-twins. We conclude that, of the dimensions analyzed, the narrow disorganized dimension shows most promise as a phenotype for molecular genetic research.