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Prefrontal inefficiency is associated with polygenic risk for schizophrenia
Esther Walton1, Daniel Geisler1, Phil H Lee
1Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany;
Schizophrenia Bulletin
|December 12, 2013
Summary
This study found that higher polygenic risk scores for schizophrenia predict reduced prefrontal cortex efficiency during working memory tasks. This highlights the cumulative impact of common genetic variants on brain function relevant to schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Schizophrenia presents with diverse symptoms and likely has a polygenic basis.
- Prefrontal cortex inefficiency during working memory is a recognized intermediate phenotype for schizophrenia.
Purpose of the Study:
- To investigate the association between polygenic risk for schizophrenia and prefrontal cortex inefficiency.
- To explore the cumulative effect of common genetic variants on a brain-based biomarker for schizophrenia.
Main Methods:
- Utilized imaging, genetic, and behavioral data from 255 participants in the Mind Clinical Imaging Consortium study.
- Calculated polygenic risk scores (PGRS) based on over 600 single nucleotide polymorphisms associated with schizophrenia.
- Analyzed neural inefficiency in the dorsolateral prefrontal cortex during working memory tasks.
Main Results:
- Increased polygenic risk for schizophrenia was significantly associated with neural inefficiency in the left dorsolateral prefrontal cortex.
- Gene ontology analysis revealed that loci contributing to polygenic risk are involved in brain development and other relevant processes.
- Findings were supported by analyses using data from the Psychiatric Genomics Consortium.
Conclusions:
- Cumulative genetic risk, reflected by polygenic risk scores, impacts a key intermediate phenotype for schizophrenia.
- The additive effects of numerous common genetic variants with small effects offer greater insight into schizophrenia's etiology than single variants.
- This research provides a deeper understanding of the genetic underpinnings of schizophrenia through its effect on brain function.
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