Impact of schizophrenia-risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals.
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.
Markov
Valentin
V
Department of Psychiatry and Psychotherapy, Medical Faculty, RWTH Aachen University, Aachen, Germany. vmarkov@ukaachen.de
Krug
Axel
A
Krach
Sören
S
Jansen
Andreas
A
Eggermann
Thomas
T
Zerres
Karl
K
Stöcker
Tony
T
Shah
N Jon
NJ
Nöthen
Markus M
MM
Treutlein
Jens
J
Rietschel
Marcella
M
Kircher
Tilo
T
D000328:Adult; D000483:Alleles; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology*; D011930:Reaction Time; D012559:Schizophrenia / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins