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Brand, Jessica (2013) DEVELOPMENTAL GENETIC ASPECTS OF SCHIZOPHRENIA, NEUREGULIN-1, AND COGNITION. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Recent work suggests potentially promising relationships between sequence variation in Neuregulin-1 (NRG1) and both schizophrenia and neurocognitive function. Cognitive deficits are very common in schizophrenia and have been shown to be familial in nature. Based on these findings, we hypothesized that cognitive deficits may be related to variation in NRG1 in an age-dependent manner during adolescence and adulthood, thus providing a possible mechanism by which NRG1 could act as a late neurodevelopmental susceptibility gene for schizophrenia.

This question was examined using individuals from 39 multigenerational multiplex families, including 58 affected participants and 361 unaffected relatives aged 15-85 years. Participants were genotyped for 36 NRG1 single nucleotide polymorphisms (SNPs) previously associated with schizophrenia. Participants completed diagnostic interviews and a computerized neurocognitive battery that assessed eight cognitive domains.

Pedigree-based variance component analyses were performed to estimate the main effects of age and individual SNPs, and the interactions between age and SNPs in predicting cognition for each domain. There were multiple nominally significant NRG1 x age interactions across several domains and markers, although few remained significant after modified Bonferroni correction. Overall, this study suggests a potential role of NRG1 x age interactions in cognitive performance within multiplex families with schizophrenia, especially within the domains of Emotional Processing, Abstraction/Mental Flexibility, Attention, and Sensorimotor Dexterity and the NRG1 markers SNP8NRG221132, SNP8NRG221533/rs35753505, rs776401, and rs1473438 that warrants further investigation.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Brand, Jessicajly14@pitt.eduJLY14
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairPogue-Geile, Michaelmfpg@pitt.eduMFPG
Committee MemberGrace, Anthonygraceaa@pitt.eduGRACEAA
Committee MemberCheong, JeeWonjcheong@pitt.eduJCHEONG
Committee MemberErikson, Kirkkiericks@pitt.eduKIERICKS
Committee MemberRoecklein, Kathrynkroeck@pitt.eduKROECK
Date: 28 September 2013
Date Type: Publication
Defense Date: 30 April 2012
Approval Date: 28 September 2013
Submission Date: 8 June 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 160
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Psychology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Schizophrenia, Neuregulin-1, NRG1, neurocognitive function
Date Deposited: 28 Sep 2013 21:23
Last Modified: 28 Sep 2018 05:15


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