COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET.
A common polymorphism (val158met) in the gene encoding catechol-O-methyltransferase (COMT) has been shown to affect dopamine (DA) tone in cortex and cortical functioning. D1 receptors are the main DA receptors in the cortex, and studies have shown that decreased levels of cortical DA are associated with upregulation of D1 receptor availability, as measured with the positron-emission tomography (PET) radiotracer [11C]NNC112. We compared [11C]NNC 112 binding in healthy volunteers homozygous for the Val allele compared with Met carriers. Subjects were otherwise matched for parameters known to affect [11C]NNC 112 binding. Subjects with Val/Val alleles had significantly higher cortical [11C]NNC 112 binding compared with Met carriers, but did not differ in striatal binding. These results confirm the prominent role of COMT in regulating DA transmission in cortex but not striatum, and the reliability of [11C]NNC 112 as a marker for low DA tone as previously suggested by studies in patients with schizophrenia.
Slifstein
M
M
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. mms218@columbia.edu
Kolachana
B
B
Simpson
E H
EH
Tabares
P
P
Cheng
B
B
Duvall
M
M
Frankle
W Gordon
WG
Weinberger
D R
DR
Laruelle
M
M
Abi-Dargham
A
A
D000328:Adult; D019943:Amino Acid Substitution; D001552:Benzazepines; D001572:Benzofurans; D001931:Brain Mapping / Q000379:methods; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008032:Limbic System / Q000502:physiology*; D008297:Male; D008487:Medical History Taking; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000502:physiology*
D001552:Benzazepines; D001572:Benzofurans; D017447:Receptors, Dopamine D1; C077123:NNC 112; D002394:Catechol O-Methyltransferase