Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with differences in frontal brain activation in a working memory task in healthy individuals.
Working memory dysfunctions are a prominent feature in schizophrenia. These impairments have been linked to alterations in prefrontal brain activation with studies reporting hypo- and hyperactivations. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes modulate working memory and its neural correlates. The aim of the present study was to test the influence of the NRG1 schizophrenia susceptibility gene on working memory and its neural correlates in healthy subjects. 429 healthy individuals performed a verbal and a spatial working memory task. A subsample of 85 subjects performed a 2-back version of the Continuous Performance Test (CPT) in a functional MRI study. The NRG1 SNP8NRG221533 (rs35753505) carrier status was determined and correlated with working memory performance and brain activation. There were no effects of genetic status on behavioural performance in the working memory tasks in the 429 subjects and in the fMRI task (n=85). A linear effect of NRG1 SNP8NRG221533 carrier status on neuronal activation emerged in the fMRI experiment. Hyperactivation of the superior frontal gyrus (BA 10) was correlated with the number of risk alleles. The fMRI data suggest that performance measures between groups did not differ due to a compensational activation of BA 10 in risk-allele carriers. Our results are in line with functional imaging studies in patients with schizophrenia, which also showed a differential activation in lateral prefrontal areas.
Krug
Axel
A
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany. akrug@ukaachen.de
Markov
Valentin
V
Eggermann
Thomas
T
Krach
Sören
S
Zerres
Klaus
K
Stöcker
Tony
T
Shah
N Jon
NJ
Schneider
Frank
F
Nöthen
Markus M
MM
Treutlein
Jens
J
Rietschel
Marcella
M
Kircher
Tilo
T
D000293:Adolescent; D000328:Adult; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D011939:Mental Recall; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*; D013647:Task Performance and Analysis; D055815:Young Adult
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1