Naslov
“ Kraepelinian” and “ Bleulerian” schizophrenia: A genetic dissection of a cognitive endophenotype

Autori
Jablensky, A ; Hallmayer, J ; Dragović, Milan ; Badcock, J ; Kalaydjieva, L.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
The Annual Genemapers conference

Mjesto i datum
Fremantle, Australija, 2004

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
schizophrenia; genetic linkage; endophenotypes; cognition

Sažetak
Cognitive deficit was conceived by Emil Kraepelin (1919) to be a core feature of a single disease, 'dementia praecox'. In contrast, Eugen Bleuler (1923) hypothesised that schizophrenia was the "common final pathway" for an aetiologically mixed group of disorders. The controversy engendered by these two great clinicians survives unscathed into the present diagnostic concepts of schizophrenia. Since schizophrenia is clinically heteogeneous and genetically complex, ICD-10 and DSM-IV diagnoses may not provide the optimal phenotypes for genetic analysis. We explored a novel, enodphenotype-based approach in the search for susceptibility genes by generating a composite quantitative phenotype which integrates multiple measurements of neurocognitive performance in the domains of attention, working memory, verbal learning, speed of information processing and personality dimensions, using a variant of latent class analysis known as Grade of Membership (GoM). The Western Australian family sample (N = 97 ; 386 individuals) used in this analysis yielded two distinct neurocognitive and clinical phenotypes, each correlated with schizophrenia: one indexing severe neurocognitive deficit and predominantly 'negative' symptoms ; and one neurocognitivelly unimpaired, with florid 'positive' psychotic symptoms. The composite neurocognitive trait was used in linkage analysis as a liability covariate, on which each individual in the sample (affected and unaffected) was assigned a score. A 10cM genome scan, followed by ordered sets analysis (OSA) resulted in consistent, significant or suggestive linkage signals for the neurocognitive deficit subtype in several genome regions (6p, 10p, and 10q ; no comparably consistent findings have yet obtained for the neurocognitivelly unimpaired subtype, suggesting a greater genetic heterogeneity. These results support "splitting" schizophrenia into aetiological distinct subtypes and demonstrate an increase in power resulting from use of composite quantitative endophenotypes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija

POVEZANOST RADA