The effects of a DTNBP1 gene variant on attention networks: an fMRI study.
BACKGROUND
Attention deficits belong to the main cognitive symptoms of schizophrenia and come along with altered neural activity in previously described cerebral networks. Given the high heritability of schizophrenia the question arises if impaired function of these networks is modulated by susceptibility genes and detectable in healthy risk allele carriers.


METHODS
The present event-related fMRI study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 of the DTNBP1 (dystrobrevin-binding protein 1) gene on brain activity in 80 subjects while performing the attention network test (ANT). In this reaction time task three domains of attention are probed simultaneously: alerting, orienting and executive control of attention.


RESULTS
Risk allele carriers showed impaired performance in the executive control condition associated with reduced neural activity in the left superior frontal gyrus [Brodmann area (BA) 9]. Risk allele carriers did not show alterations in the alerting and orienting networks.


CONCLUSIONS
BA 9 is a key region of schizophrenia pathology and belongs to a network that has been shown previously to be involved in impaired executive control mechanisms in schizophrenia. Our results identified the impact of DTNBP1 on the development of a specific attention deficit via modulation of a left prefrontal network.
Thimm
Markus
M
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany. mthimm@ukaachen.de
Krug
Axel
A
Kellermann
Thilo
T
Markov
Valentin
V
Krach
Sören
S
Jansen
Andreas
A
Zerres
Klaus
K
Eggermann
Thomas
T
Stöcker
Tony
T
Shah
N Jon
NJ
Nöthen
Markus M
MM
Rietschel
Marcella
M
Kircher
Tilo
T
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011930:Reaction Time / Q000235:genetics / Q000502:physiology
C111539:DTNB protein, human; D049029:Dystrophin-Associated Proteins; D009479:Neuropeptides