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Genetic Variation in Cognitive Flexibility Performance and Brain Activation in Schizophrenia: A Multiplex Extended Pedigree Study

Rupert, Petra (2020) Genetic Variation in Cognitive Flexibility Performance and Brain Activation in Schizophrenia: A Multiplex Extended Pedigree Study. Master's Thesis, University of Pittsburgh. (Unpublished)

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On executive tasks of cognitive flexibility, individuals with schizophrenia have poorer performance and often differing patterns of brain activation. The present study sought to examine the degree to which cognitive flexibility performance and its related brain activation may reflect effects of schizophrenia genetic risk using an extended pedigree design. A total of 521 participants, 30 schizophrenia probands, 202 of their relatives (1st to 4th degree), 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. Both behavioral performances and brain activation during the task in five regions of interest were analyzed. In order to examine diagnostic specificity, we also investigated genetic correlations between diagnosed depression and PCET performance and brain activation. Cognitive flexibility performance was significantly genetically correlated with schizophrenia both out of (Rg=-0.65, p=0.005) and in the scanner (Rg=-0.56, p<0.001) after false discovery rate (FDR) correction. In contrast, genetic correlations between schizophrenia and ROI brain activation in the Frontal Pole (right Rg=0.30, p=0.30, left Rg=1.00, p=0.01), Anterior Cingulate Gyrus (bilateral Rg=0.39, p=0.18), and Middle Frontal Gyrus (right Rg=1.00, p=0.04, left Rg=0.60, p=0.12) were either not nominally significant or were not significant after FDR correction. Neither behavioral performance nor brain activation measures were significantly genetically correlated with depression. In contrast to some hypotheses, these results suggest that behavioral performance on this measure of cognitive flexibility (PCET) is more sensitive (and also specific compared with depression) to schizophrenia genetic risk effects than fMRI measures of its regional brain activation.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Rupert, Petraper29@pitt.eduper29
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberRoalf, David
Committee MemberErickson, Kirk
Committee MemberPrasad, Konasale
Committee ChairPogue-Geile, Michael
Date: 16 September 2020
Date Type: Publication
Defense Date: 4 August 2020
Approval Date: 16 September 2020
Submission Date: 6 August 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 52
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Psychology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: schizophrenia; fMRI; genetic correlation; cognitive flexibility
Date Deposited: 16 Sep 2020 16:02
Last Modified: 16 Sep 2022 05:15


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