Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia.
Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism of COMT, Val(108/158) Met, affects prefrontal function, and the high-activity Val allele has been reported to be a genetic risk factor for schizophrenia. We used in situ hybridization histochemistry to measure mRNA levels of COMT in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia (N=14) and of normal controls (N=15). While the groups did not differ in terms of mean level of COMT mRNA, there was a significantly different laminar pattern of COMT mRNA expression in pyramidal neurons (F=2.68, df=4,108, P <0.04); patients with schizophrenia had relatively lower levels in the superficial (II/III) layers and higher levels in the intermediate/deep (IV/V) layers (P&<0.01), while in controls, the expression was homogeneous across layers. Neither the mean level nor the laminar distribution of COMT mRNA was related to the Val(108/158) Met genotype, suggesting that the feedback regulation of mRNA level is not a compensation for the functional effect of the COMT polymorphism. The disease-related laminar difference of COMT expression may be involved in dysregulation of dopamine signaling circuits in the DLPFC of patients with schizophrenia.
Matsumoto
Mitsuyuki
M
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA. matsum_m@yamanouchi.co.jp
Weickert
Cynthia Shannon
CS
Beltaifa
Senda
S
Kolachana
Bhaskar
B
Chen
Jingshan
J
Hyde
Thomas M
TM
Herman
Mary M
MM
Weinberger
Daniel R
DR
Kleinman
Joel E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics
D012333:RNA, Messenger; D002394:Catechol O-Methyltransferase