Catechol-o-Methyltransferase Enzyme Activity and Protein Expression in Human Prefrontal Cortex across the Postnatal Lifespan
Abstract
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 (Val(158)Met) 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 Val(158)Met 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.
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- Authors
- Tunbridge, E., Weickert, C., Kleinman, J., Herman, M., Chen, J., Kolachana, B., Harrison, P., & Weinberger, D.
- Affiliations
- National Institutes of Health (US)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-11
- Volume
- 17
- Issue
- 5
- Pages
- 1206-1212
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2131510354
- Cited by
- 197
- References
- 40
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2022: 6 · 2021: 3 · 2020: 44 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 10 · 2013: 10 · 2012: 17
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- catechol-O-methyltransferase, prefrontal cortex, postnatal development, human lifespan, dopaminergic modulation, COMT Val158Met polymorphism, aging
- MeSH terms
- Adolescent, Adult, Aged, Aging, Catechol O-Methyltransferase, Dopamine, Enzyme Activation, Female, Humans, Infant, Infant, Newborn, Male, Gene Expression Regulation, Enzymologic, Prefrontal Cortex, Gene Expression Regulation, Developmental
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