Genetic markers of striatal dopamine predict individual differences in dysfunctional, but not functional impulsivity
Abstract
Various psychiatric disorders are characterized by elevated levels of impulsivity. Although extensive evidence supports a specific role of striatal, but not frontal dopamine (DA) in human impulsivity, recent studies on genetic variability have raised some doubts on such a role. Importantly, impulsivity consists of two dissociable components that previous studies have failed to separate: functional and dysfunctional impulsivity. We compared participants with a genetic predisposition to have relatively high striatal DA levels (DAT1 9-repeat carriers, DRD2 C957T T/T homozygotes, and DRD4 7-repeat carriers) with participants with other genetic predispositions. We predicted that the first group would show high scores of dysfunctional, but not functional, self-reported impulsivity and greater difficulty in inhibiting a behavioral response to a stop-signal, a behavioral measure of impulsivity. In a sample of 130 healthy adults, we studied the relation between DAT1, DRD4, and C957T polymorphism at the DRD2 gene (polymorphisms related to striatal DA) and catechol-Omethyltransferase (COMT) Val158Met (a polymorphism related to frontal DA) on self-reported dysfunctional and functional impulsivity, assessed by the Dickman impulsivity inventory (DII), and the efficiency of inhibitory control, assessed by the stop-signal paradigm. DRD2 C957T T/T homozygotes and DRD4 7-repeat carriers indeed had significantly higher scores on self-reported dysfunctional, but not functional, impulsivity. T/T homozygotes were also less efficient in inhibiting prepotent responses. Our findings support the claim that dopaminergic variation affects dysfunctional impulsivity. This is in line with the notion that the over-supply of striatal DA might weaken inhibitory pathways, thereby enhancing the activation of, and the competition between responses.
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A second polymorphism associated with decreased cortical and thalamic D2-receptor availability is related to poor action cancelation.
“A second polymorphism, which has been associated with decreased cortical and thalamic D2-receptor availability (Hirvonen et al., 2009), was also related to poor action cancelation (Colzato et al., 2010).”
From Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders (2014) · cites this paper as Colzato et al., 2010
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- Authors
- Colzato, L. S., van den Wildenberg, W. P. M., Van der Does, A. J. W., & Hommel, B.
- Affiliations
- Leiden University (NL)
- Corresponding author
- Colzato, L.S.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 170
- Issue
- 3
- Pages
- 782-788
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2143738475
- Cited by
- 117
- References
- 72
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 2 · 2018: 7 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 20 · 2013: 8 · 2012: 12
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Funders
- Netherlands Organization for Scientific Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- dysfunctional impulsivity, functional impulsivity, striatal dopamine, COMT Val158Met polymorphism, inhibitory control, stop-signal task, genetic susceptibility, individual differences, response inhibition
- MeSH terms
- Adult, Catechol O-Methyltransferase, Corpus Striatum, Dopamine, Female, Genetic Markers, Humans, Impulsive Behavior, Inhibition, Psychological, Intelligence, Male, Polymorphism, Genetic, Receptors, Dopamine D2, Genetic Predisposition to Disease, Dopamine Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Self Report
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