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Subtyping schizophrenia: implications for genetic research

Abstract

Phenotypic variability and likely extensive genetic heterogeneity have been confounding the search for the causes of schizophrenia since the inception of the diagnostic category. The inconsistent results of genetic linkage and association studies using the diagnostic category as the sole schizophrenia phenotype suggest that the current broad concept of schizophrenia does not demarcate a homogeneous disease entity. Approaches involving subtyping and stratification by covariates to reduce heterogeneity have been successful in the genetic study of other complex disorders, but rarely applied in schizophrenia research. This article reviews past and present attempts at delineating schizophrenia subtypes based on clinical features, statistically derived measures, putative genetic indicators, and intermediate phenotypes, highlighting the potential utility of multidomain neurocognitive endophenotypes.

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Acknowledgements

Work on the Western Australian Family Study of Schizophrenia has been supported by grants (to AJ) from the National Health and Medical Research Council, Australia, and the North Metropolitan Health Services, Perth, Western Australia. Invaluable assistance with the bibliography and illustrations for this review was provided by Lyn Kløve, Milan Dragović and Vera Morgan.

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Jablensky, A. Subtyping schizophrenia: implications for genetic research. Mol Psychiatry 11, 815–836 (2006). https://doi.org/10.1038/sj.mp.4001857

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