Journal article
Cumulative Genetic Risk and Prefrontal Activity in Patients With Schizophrenia
Schizophrenia bulletin, Vol.39(3), pp.703-711
05/2013
DOI: 10.1093/schbul/sbr190
PMCID: PMC3627773
PMID: 22267534
Abstract
The lack of consistency of genetic associations in highly heritable mental illnesses, such as schizophrenia, remains a challenge in molecular psychiatry. Because clinical phenotypes for psychiatric disorders are often ill defined, considerable effort has been made to relate genetic polymorphisms to underlying physiological aspects of schizophrenia (so called intermediate phenotypes), that may be more reliable. Given the polygenic etiology of schizophrenia, the aim of this work was to form a measure of cumulative genetic risk and study its effect on neural activity during working memory (WM) using functional magnetic resonance imaging. Neural activity during the Sternberg Item Recognition Paradigm was measured in 79 schizophrenia patients and 99 healthy controls. Participants were genotyped, and a genetic risk score (GRS), which combined the additive effects of 41 single-nucleotide polymorphisms (SNPs) from 34 risk genes for schizophrenia, was calculated. These risk SNPs were chosen according to the continuously updated meta-analysis of genetic studies on schizophrenia available at
www.schizophreniaresearchforum.org
. We found a positive relationship between GRS and left dorsolateral prefrontal cortex inefficiency during WM processing. GRS was not correlated with age, performance, intelligence, or medication effects and did not differ between acquisition sites, gender, or diagnostic groups. Our study suggests that cumulative genetic risk, combining the impact of many genes with small effects, is associated with a known brain-based intermediate phenotype for schizophrenia. The GRS approach could provide an advantage over studying single genes in studies focusing on the genetic basis of polygenic conditions such as neuropsychiatric disorders.
Details
- Title: Subtitle
- Cumulative Genetic Risk and Prefrontal Activity in Patients With Schizophrenia
- Creators
- Esther Walton - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMJessica Turner - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMRandy L Gollub - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMDara S Manoach - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMAnastasia Yendiki - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMBeng-Choon Ho - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMScott R Sponheim - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMVince D Calhoun - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NMStefan Ehrlich - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM
- Resource Type
- Journal article
- Publication Details
- Schizophrenia bulletin, Vol.39(3), pp.703-711
- Publisher
- Oxford University Press
- DOI
- 10.1093/schbul/sbr190
- PMID
- 22267534
- PMCID
- PMC3627773
- ISSN
- 0586-7614
- eISSN
- 1745-1701
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003427902771
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