Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene
Abstract
UNLABELLED: The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry. OBJECTIVES: The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance. METHODS: College-age participants (N=199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA. RESULTS: Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin 1B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10). CONCLUSIONS: A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.
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Individuals homozygous for the T-allele of a polymorphism in the TPH-2 gene show increased SSRT in the Stop-signal task.
“Individuals homozygous for the T-allele of a polymorphism in the TPH-2 gene showed increased SSRT in the Stop-signal task (Stoltenberg et al., 2006).”
From Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders (2014) · cites this paper as Stoltenberg et al., 2006
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- Authors
- Stoltenberg, S. F., Glass, J. M., Chermack, S. T., Flynn, H. A., Li, S., Weston, M. E., & Burmeister, M.
- Affiliations
- National Institute on Alcohol Abuse and Alcoholism (US)
- University of Michigan (US)
- Corresponding author
- Stoltenberg, Scott F.
- Venue
- Psychiatric Genetics
- Published
- 2006-02
- Volume
- 16
- Issue
- 1
- Pages
- 35-38
- ISSN
- 0955-8829 (ISSN-L)
- OpenAlex
- W2148926613
- Cited by
- 62
- References
- 36
- Citations by year
- 2023: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA000295)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- response inhibition, tryptophan hydroxylase 2, TPH2 gene, stop-signal task, serotonergic system, impulsivity, dorsal raphe nucleus, serotonin synthesis, monoamine oxidase A, sex differences, genetic association
- MeSH terms
- Adult, Alleles, Analysis of Variance, Base Sequence, Brain, Female, Gene Frequency, Humans, Male, Surveys and Questionnaires, Reaction Time, Serotonin, Task Performance and Analysis, Tryptophan Hydroxylase, DNA Primers, Polymorphism, Single Nucleotide
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