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Cited by 769Neurotransmitter Receptor Influence on BehaviorPharmacogenetics and Drug MetabolismSchizophrenia research and treatment

The DOI matches its Crossref record; 168 of the 173 references it cites were found in a registry or an index.

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

Bilder, Robert M, Volavka, Jan, Lachman, Herbert M, Grace, Anthony A·2004·Neuropsychopharmacology
DOI 10.1038/sj.npp.1300542
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Abstract

Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or detrimental depending on the phenotype, a range of endogenous factors, and environmental exigencies. The literature on phenotypic associations of the COMT Val158Met polymorphism is reviewed, highlighting areas where this hypothesis may have explanatory value, and pointing to possible directions for refinement of relevant phenotypes and experimental evaluation of this hypothesis.

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Research works printed but not linked: 9

  1. Bilder RM, Lipschutz-Broch L, Reiter G, Mayerhoff DI, Geisler SH, Lieberman JA (1992). A verbal learning deficit in first episode schizophrenia. J Clin Exp Neuropsychol 14: 122–124.
  2. Gunduz H, Zuffante P, Wu H, Crandall D, Szeszko P, Alvir J et al (1999). Longitudinal follow-up of superior temporal gyrus gray matter in first-episode schizophrenia. Schizophr Res 36: 199.
  3. Hawi Z, Millar N, Daly G, Fitzgerald M, Gill M (2000). No association between catechol-O-methyltransferase (COMT) gene polymorphism and attention deficit hyperactivity disorder (ADHD) in an Irish sample. Am J Med Genet 96: 282–284. · DOI · Paper page
  4. Kotler M, Barak P, Cohen H, Averbuch IE, Grinshpoon A, Gritsenko I et al (1999). Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity. Am J Med Genet 88: 628–633. · DOI
  5. McDougle CJ, Goodman WK, Price LH (1994b). Dopamine antagonists in tic-related and psychotic spectrum obsessive–compulsive disorder. J Clin Psychiatry 55(Suppl): 24–31.
  6. Paulus MP, Bilder RM, Lieberman JA (1999). Complex dysregulation in sequential organization and dysregulation in dopaminergic modulation in first episode schizophrenia patients. In: Prahdan N, Rapp PE, Sreenivasan R (eds). Nonlinear Dynamics and Brain Functioning. Nova: Huntington, NY.
  7. Pribram KH (1987). The subdivisions of the frontal cortex revisited. In Perecman E (ed) The Frontal Lobes Revisited. IRBN Press: New York. pp 11–39.
  8. Schindler KM, Richter MA, Kennedy JL, Pato MT, Pato CN (2000). Association between homozygosity at the COMT gene locus and obsessive–compulsive disorder. Am J Med Genet 96: 721–724. · DOI
  9. Tahir E, Curran S, Yazgan Y, Ozbay F, Cirakoglu B, Asherson PJ (2000). No association between low- and high-activity catecholamine-methyl-transferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Am J Med Genet 96: 285–288. · DOI · Paper page

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Metadata

Authors
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A.
Affiliations
  • University of California, Los Angeles (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • Albert Einstein College of Medicine (US)
  • University of Pittsburgh (US)
Corresponding author
Bilder, Robert M
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2004-08-11
Volume
29
Issue
11
Pages
1943-1961
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/sj.npp.1300542
OpenAlex
W1997343027
Cited by
769
References
173
Citations by year
2026: 3 · 2025: 5 · 2024: 16 · 2023: 20 · 2022: 21 · 2021: 45 · 2020: 20 · 2019: 23 · 2018: 32 · 2017: 34 · 2016: 36 · 2015: 42 · 2014: 57 · 2013: 60 · 2012: 64
FWCI
2.35
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Alliance for Research on Schizophrenia and Depression
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
catechol-O-methyltransferase, COMT Val158Met polymorphism, tonic dopamine, phasic dopamine, dopamine D1 receptor, working memory, executive function, neuropsychiatric phenotypes
MeSH terms
Animals, Mental Disorders, Catechol O-Methyltransferase, Dopamine, Humans, Phenotype, Polymorphism, Genetic

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