Home Random Page



The Western Australian family study of schizophrenia

The Western Australian family study of schizophrenia (WAFSS) was designed as a testbed for exploring heterogeneity in schizophrenia, delineating genetic variants, or subtypes, and putting them to the test of genetic linkage analysis. Our group adopted from the outset the conjecture that: (a) the broad syndrome of schizophrenia is a conflation of several underlying disorders that may be aetiologically distinct; and (b) endophenotypes anchored in objective measures of brain dysfunction might separate out such disorders more clearly than clinical symptoms alone. The available evidence was pointing to cognitive and neurobehavioural measures as being particularly sensitive to dysfunction associated with schizophrenia, as well as being longitudinally stable, state-independent, and heritable. As most neurocognitive tasks typically engage several component processes, we reasoned that a linear composite of such variables would be an appropriate endophenotype for genetic studies and developed a design allowing simultaneous analysis of performance in the various cognitive domains for shared patterns of dysfunction, rather than for isolated deficits.

In this study, involving 112 families (388 members, of which 138 affected with schizophrenia or schizophrenia spectrum disorders) and 143 population controls, we employed a comprehensive clinical and cognitive assessment protocol243 to evaluate patients, first-degree relatives, and controls. The test results were analysed for complex patterns of dysfunction using a GoM model, a form of latent structure analysis which defines a parsimonious number of latent groups or patterns of responses ('pure types'), allowing individuals to resemble each group to varying degrees, rather than allocating them to mutually exclusive clusters as performed in standard LCA.149, 150 GoM resolves sample heterogeneity by assigning to each individual GoM scores of affinity to each one of several pure types. The resulting classification identified two distinct pure types of multivariate neurocognitive profiles (Figure 1), which comprised over 90% of the schizophrenia patients in the sample, as well as 23% of their clinically unaffected first-degree relatives: a cognitive deficit (CD) subtype and a cognitively spared (CS) subtype. In the CD subtype verbal memory impairment was the most consistently observed cognitive deficit. Multiple (3+) cognitive deficits were exhibited by all CD cases, and estimated current IQ was low in the majority of these patients. Consequently, generalized cognitive deficiency was the most salient characteristic of this subtype, in contrast to mild or patchy deficits in the CS subtype.

Figure 1.

Profiles of the two cognitive subtypes (CD and CS), identified in the Western Australian Family Study of Schizophrenia.243

Full figure and legend (58K)



Date: 2016-04-22; view: 152

<== previous page | next page ==>
Subtypes of cognitive dysfunction | Subtyping schizophrenia: implications for genetic research
doclecture.net - lectures - 2014-2017 year. (0.006 sec.)