TY - JOUR
T1 - Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia
AU - Matsumoto, Mitsuyuki
AU - Weickert, Cynthia Shannon
AU - Beltaifa, Senda
AU - Kolachana, Bhaskar
AU - Chen, Jingshan
AU - Hyde, Thomas M.
AU - Herman, Mary M.
AU - Weinberger, Daniel R.
AU - Kleinman, Joel E.
PY - 2003/8
Y1 - 2003/8
N2 - Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism of COMT, Val108/158 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 Val108/158 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.
AB - Human prefrontal cortical neurons express catechol O-methyltransferase (COMT), an enzyme that inactivates the neurotransmitter dopamine. A functional polymorphism of COMT, Val108/158 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 Val108/158 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.
KW - Cortical layer
KW - DLPFC
KW - Dopamine
KW - Functional Val/Met polymorphism
KW - Human brain
KW - In situ hybridization histochemistry
KW - Pyramidal neuron
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U2 - 10.1038/sj.npp.1300218
DO - 10.1038/sj.npp.1300218
M3 - Article
C2 - 12799619
AN - SCOPUS:0041884746
SN - 0893-133X
VL - 28
SP - 1521
EP - 1530
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 8
ER -