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32. Effects of schizophrenia genetic risk on multi-modal assessment of cognitive flexibility: A multiplex extended pedigree study.
Although important advances have been made, improving our understanding of the nature of genetic risk for schizophrenia is crucial. Therefore, this study focuses on examining the effects of aggregate genetic risk for schizophrenia on cognitive flexibility as a potential endophenotype. A total of 523 participants, 31 schizophrenia probands, 203 of their relatives, and 289 unrelated controls completed similar versions of a computerized cognitive flexibility task (Penn Conditional Exclusion Test) both out of and in an MRI scanner during a functional imaging sequence (r=0.43, p<.001). Heritability of cognitive flexibility performance as well as the genetic correlation of performance and schizophrenia were computed. While heritability of cognitive flexibility was not significant out of the scanner (h2=0.10; p=0.3), heritability was significant for the version completed within the scanner (h2=0.43, p<.001). Cognitive flexibility was significantly genetically correlated with schizophrenia, both out of (Rg=-1.0, p=.03) and in the MRI (Rg=-.84, p=0.01). These results suggest that schizophrenia genetic risk affects cognitive flexibility performance, measured by versions of the PCET both out of and within an MRI scanner, further justifying examination of brain activation during the task. Analyses of the heritability and genetic correlation with schizophrenia of changes in fMRI brain activity during the PCET task are ongoing.