Polygenic risk for schizophrenia affects working memory and its neural correlates in healthy subjects

Schizophrenia is a disorder with a high heritability. Patients as well as their first degree relatives display lower levels of performance in a number of cognitive domains compared to subjects without genetic risk. Several studies could link these aberrations to single genetic variants, however, onl...

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Main Authors: Krug, Axel (Author) , Rietschel, Marcella (Author) , Witt, Stephanie (Author)
Format: Article (Journal)
Language:English
Published: July 2018
In: Schizophrenia research
Year: 2018, Volume: 197, Pages: 315-320
ISSN:1573-2509
DOI:10.1016/j.schres.2018.01.013
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.schres.2018.01.013
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0920996418300331
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Author Notes:Axel Krug, Bruno Dietsche, Rebecca Zöllner, Dilara Yüksel, Markus M. Nöthen, Andreas J. Forstner, Marcella Rietschel, Udo Dannlowski, Bernhard T. Baune, Robert Maier, Stephanie H. Witt, Tilo Kircher

MARC

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520 |a Schizophrenia is a disorder with a high heritability. Patients as well as their first degree relatives display lower levels of performance in a number of cognitive domains compared to subjects without genetic risk. Several studies could link these aberrations to single genetic variants, however, only recently, polygenic risk scores as proxies for genetic risk have been associated with cognitive domains and their neural correlates. In the present study, a sample of healthy subjects (n=137) performed a letter version of the n-back task while scanned with 3-T fMRI. All subjects were genotyped with the PsychChip and polygenic risk scores were calculated based on the PGC2 schizophrenia GWAS results. Polygenic risk for schizophrenia was associated with a lower degree of brain activation in prefrontal areas during the 3-back compared to the 0-back baseline condition. Furthermore, polygenic risk was associated with lower levels of brain activation in the right inferior frontal gyrus during the 3-back compared to a 2-back condition. Polygenic risk leads to a shift in the underlying activation pattern to the left side, thus resembling results reported in patients with schizophrenia. The data may point to polygenic risk for schizophrenia being associated with brain function in a cognitive task known to be impaired in patients and their relatives. 
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