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Donohoe G, Morris DW, Clarke S, McGhee KA, Schwaiger S, Nangle JM, Garavan H, Robertson IH, Gill M, Corvin A. Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study. Neuropsychologia. 2007 Jan 28 ; 45(2):454-8. Pubmed Abstract

Comments on News and Primary Papers

Primary Papers: Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study.

Comment by:  Katherine E. Burdick
Submitted 1 September 2006
Posted 1 September 2006

This interesting study by Donohoe and colleagues examined the relationship between genetic variation in the DTNBP1 gene and cognition in a sample of 52 individuals with schizophrenia. The authors report a significant association between spatial working memory and a risk haplotype that had previously been identified in their sample.

As noted by the authors, this study adds to a growing literature focused on the genetics of cognition, each contributing to the advancement of our knowledge of the genetic underpinnings of neurocognitive function as it relates to both normal and psychiatric subjects. Like schizophrenia, neurocognition is a highly complex phenotype, within which lie a number of more specific phenotypes, with a shared variance across domains. Our previous work with DTNBP1, which demonstrated an association with the component of neurocognition that represents this shared variance, implies a generalized effect of DTNBP1 on all, or most, measures of neurocognition in healthy subjects and patients with schizophrenia (Burdick et al., 2006). This is not in conflict with the Donohoe finding, as it is likely that DTNBP1ís effects are not equivalent across all neurocognitive domains. In fact, in the Irish cohort, differences between carriers and non-carriers on a number of other measures (e.g., Paired Associate Learning; ID/ED) had effect sizes in the moderate range, which may suggest that given a larger sample, a more generalized effect on neurocognition might emerge as statistically significant. It is also likely, as noted by the authors, that the psychometric properties of specific tasks contribute to discrepant results (i.e., different measures of neurocognitive function are differentially sensitive to genetic effects).

Given the fact that a functional variant has not yet been identified within DTNBP1, each investigation into its actions on behavioral phenotypes is important and may bring us a step closer to determining the mechanism through which DTNBP1 increases the risk for developing schizophrenia.

View all comments by Katherine E. Burdick