Effect of catechol-O-methyltransferase val158met genotype on attentional control.
The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control (AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase (COMT). A functional polymorphism (val158met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val158met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("val") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC.
Blasi
Giuseppe
G
Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1379, USA.
Mattay
Venkata S
VS
Bertolino
Alessandro
A
Elvevåg
Brita
B
Callicott
Joseph H
JH
Das
Saumitra
S
Kolachana
Bhaskar S
BS
Egan
Michael F
MF
Goldberg
Terry E
TE
Weinberger
Daniel R
DR
D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000502:physiology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000098:blood supply / Q000502:physiology*; D011930:Reaction Time / Q000235:genetics; D012044:Regression Analysis; D014633:Valine / Q000235:genetics*
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D010100:Oxygen