Catechol-o-methyltransferase valine(158)methionine genotype and resting regional cerebral blood flow in medication-free patients with schizophrenia.
BACKGROUND
A valine(158)methionine (val(158)met) polymorphism in catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with schizophrenia. Consistent with schizophrenia itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in schizophrenia have not yet been characterized.


METHODS
Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the COMT val(158)met polymorphism and underwent two 60-second radiolabeled water ([(15)O]H(2)O) regional cerebral blood flow (rCBF) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate.


RESULTS
In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus.


CONCLUSIONS
In schizophrenia, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity.
Eisenberg
Daniel Paul
DP
Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland 20892-1365, USA.
Sarpal
Deepak
D
Kohn
Philip D
PD
Meyer-Lindenberg
Andreas
A
Wint
Dylan
D
Kolachana
Bhaskar
B
Apud
José
J
Weinberger
Daniel R
DR
Berman
Karen Faith
KF
D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D012146:Rest / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013223:Statistics as Topic; D014633:Valine / Q000235:genetics*; D055815:Young Adult
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine