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Genetic variation in G72 correlates with brain activation in the right middle temporal gyrus in a verbal fluency task in healthy individuals.

Abstract
The D-amino acid oxidase activator gene (G72) has been found associated with several psychiatric disorders such as schizophrenia, major depression, and bipolar disorder. Impaired performance in verbal fluency tasks is an often replicated finding in the mentioned disorders. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and lateral temporal areas and could possibly constitute an endophenotype. Therefore, it is of interest whether genes associated with the disorders, such as G72, modulate verbal fluency performance and its neural correlates. Ninety-six healthy individuals performed a semantic verbal fluency task while brain activation was measured with functional MRI. All subjects were genotyped for two single nucleotide polymorphisms (SNP) in the G72 gene, M23 (rs3918342) and M24 (rs1421292), that have previously shown association with the above-mentioned disorders. The effect of genotype on brain activation was assessed with fMRI during a semantic verbal fluency task. Although there were no differences in performance, brain activation in the right middle temporal gyrus (BA 39) and the right precuneus (BA 7) was positively correlated with the number of M24 risk alleles in the G72 gene. G72 genotype does modulate brain activation during language production on a semantic level in key language areas. These findings are in line with structural and functional imaging studies in schizophrenia, which showed alterations in the right middle temporal gyrus.
AuthorsAxel Krug, Valentin Markov, Sören Krach, Andreas Jansen, Klaus Zerres, Thomas Eggermann, Tony Stöcker, N Jon Shah, Markus M Nöthen, Alexander Georgi, Jana Strohmaier, Marcella Rietschel, Tilo Kircher
JournalHuman brain mapping (Hum Brain Mapp) Vol. 32 Issue 1 Pg. 118-26 (Jan 2011) ISSN: 1097-0193 [Electronic] United States
PMID20336655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightHum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.
Chemical References
  • Carrier Proteins
  • DAOA protein, human
  • Intracellular Signaling Peptides and Proteins
Topics
  • Adolescent
  • Adult
  • Alleles
  • Brain Mapping
  • Carrier Proteins (genetics)
  • Endophenotypes
  • Female
  • Functional Laterality (physiology)
  • Genetic Variation
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Intracellular Signaling Peptides and Proteins
  • Language
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Speech (physiology)
  • Surveys and Questionnaires
  • Temporal Lobe (physiology)

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