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Cerebral Cortex Advance Access originally published online on July 11, 2006
Cerebral Cortex 2007 17(5):1206-1212; doi:10.1093/cercor/bhl032
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Published by Oxford University Press 2006.

Catechol-o-Methyltransferase Enzyme Activity and Protein Expression in Human Prefrontal Cortex across the Postnatal Lifespan

EM Tunbridge1, CS Weickert2, JE Kleinman2, MM Herman2, J Chen2, BS Kolachana2, PJ Harrison1 and DR Weinberger2

1 Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK, 2 Genes, Cognition and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, USA

Address correspondence to Elizabeth M. Tunbridge. Department of Psychiatry, Neurosciences Building, Oxford University, Warneford Hospital, Oxford OX3 7JX, UK. Email: elizabeth.tunbridge{at}psych.ox.ac.uk.

The prefrontal cortex (PFC) dopamine system, which is critical for modulating PFC function, undergoes remodeling until at least young adulthood in primates. Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val158Met) that has been associated with variation in PFC function. We examined COMT enzyme activity and protein immunoreactivity in the PFC during human postnatal development. Protein was extracted from PFC of normal individuals from 6 age groups: neonates (1–4 months), infants (5–11 months), teens (14–18 years), young adults (20–24 years), adults (31–43 years), and aged individuals (68–86 years; n = 5–8 per group). There was a significant 2-fold increase in COMT enzyme activity from neonate to adulthood, paralleled by increases in COMT protein immunoreactivity. Furthermore, COMT protein immunoreactivity was related to Val158Met genotype, as has been previously demonstrated. The significant increase in COMT activity from neonate to adulthood complements previous findings of protracted postnatal changes in the PFC dopamine system and may reflect an increasing importance of COMT for PFC dopamine regulation during maturation.

Key Words: COMT • development • dopamine • schizophrenia


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