Dopamine and cognitive control: Sex-by-genotype interactions influence the capacity to switch attention
Abstract
Cognitive performance in healthy persons varies widely between individuals. Sex differences in cognition are well reported, and there is an emerging body of evidence suggesting that the relationship between dopaminergic neurotransmission, implicated in many cognitive functions, is modulated by sex. Here, we examine the influence of sex and genetic variations along the dopaminergic pathway on aspects of cognitive control. A total of 415 healthy individuals, selected from an international consortium linked to Brain Research and Integrative Neuroscience Network (BRAINnet), were genotyped for two common and functional genetic variations of dopamine regulating genes: the catechol-O-methyltransferase [COMT] gene (rs4680) and the dopamine receptor D2 [DRD2] gene (rs6277). Cognitive measures were selected to explore sustained attention (using a continuous performance task), switching of attention (using a Trails B adaptation) and working memory (a visual computerised adaptation of digit span). While there were no main effects for genotype across any tasks, analyses revealed significant sex by genotype interactions for the capacity to switch attention. In relation to COMT, superior performance was noted in females with the Val/Val genotype and for DRD2, superior performance was seen for TT females and CC males. These findings highlight the importance of considering genetic variation in baseline dopamine levels in addition to sex, when considering the impact of dopamine on cognition in healthy populations. These findings also have important implications for the many neuropsychiatric disorders that implicate dopamine, cognitive changes and sex differences.
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Functional studies in adult rodent models link genetic or experimentally induced alterations in DA neuron activity, DA release, and receptor binding to transdiagnostic changes in motivation and cognitive control.
“Functional studies in adult rodent models have linked genetic or experimentally induced alterations in DA neuron activity, DA release, and receptor binding to transdiagnostic changes in motivation and cognitive control [49, 132–135].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [132]
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The cognitive connectome of men and women: a study on sex differences across three cohorts
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- Authors
- Gurvich, C., & Rossell, S. L.
- Affiliations
- The Alfred Hospital (AU)
- Corresponding author
- Gurvich, C.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 281
- Pages
- 96-101
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2036073085
- Cited by
- 33
- References
- 81
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 4
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- 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
- dopamine, cognitive control, sex differences, catechol-O-methyltransferase, COMT Val158Met polymorphism, DRD2, dopamine D2 receptor, genetic variation, attentional shift, sustained attention, working memory, sex differences in cognition
- MeSH terms
- Adolescent, Adult, Aged, Attention, Catechol O-Methyltransferase, Cognition, Dopamine, Female, Genotype, Humans, Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Reaction Time, Sex Characteristics, Receptors, Dopamine D2, Polymorphism, Single Nucleotide, Young Adult
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