Open AccessImpact of schizophrenia‐risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals
Author(s) -
Markov Valentin,
Krug Axel,
Krach Sören,
Jansen Andreas,
Eggermann Thomas,
Zerres Karl,
Stöcker Tony,
Shah N. Jon,
Nöthen Markus M.,
Treutlein Jens,
Rietschel Marcella,
Kircher Tilo
Publication year - 2010
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.20862
Subject(s) - dorsolateral prefrontal cortex , psychology , schizophrenia (object oriented programming) , neuroscience , working memory , medial frontal gyrus , prefrontal cortex , imaging genetics , middle frontal gyrus , functional magnetic resonance imaging , parahippocampal gyrus , inferior frontal gyrus , superior frontal gyrus , neuroimaging , cognition , psychiatry , temporal lobe , epilepsy
Working memory (WM) dysfunction is a hallmark feature of schizophrenia. Functional imaging studies using WM tasks have documented both prefrontal hypo‐ and hyperactivation in schizophrenia. Schizophrenia is highly heritable, and it is unclear which susceptibility genes modulate WM and its neural correlates. A strong linkage between genetic variants in the dysbindin 1 gene and schizophrenia has been demonstrated. The aim of this study was to investigate the influence of the DTNBP1 schizophrenia susceptibility gene on WM and its neural correlates in healthy individuals. Fifty‐seven right‐handed, healthy male volunteers genotyped for DTNBP1 SNP rs1018381 status were divided in heterozygous risk‐allele carriers (T/C) and homozygous noncarriers (C/C). WM was assessed by a 2‐back vs. 0‐back version of the Continuous Performance Test (CPT), while brain activation was measured with fMRI. DTNBP1 SNP rs1018381 carrier status was determined and correlated with WM performance and brain activation. Despite any differences in behavioral performance, risk‐allele carriers exhibited significantly increased activation of the bilateral middle frontal gyrus (BA 9), a part of the dorsolateral prefrontal cortex (DLPFC), compared to noncarriers. This difference did not correlate with WM performance. The fMRI data provide evidence for an influence of genetic variation in DTNBP1 gene region tagged by SNP rs1018381 on bilateral middle frontal gyrus activation during a WM task. The increased activation in these brain areas may be a consequence of “inefficient” or compensatory DLPFC cognitive control functions. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.