Functional polymorphisms in dopaminergic genes modulate neurobehavioral and neurophysiological consequences of sleep deprivation
Open accessAbstract
Abstract Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D2receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly,DAT1andDRD2genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences inDAT1andDRD2expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Adaptations in dopamine signaling may further modulate the neurobehavioral and neurophysiological consequences of sleep loss.
“Adaptations in dopamine signaling may further modulate the neurobehavioral and neurophysiological consequences of sleep loss.”
From Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations (2025) · cites this paper as [103]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Statistical Power Analysis for the Behavioral Sciences
Cohen, J. (2013) · doi:10.4324/9780203771587 · Cited by 25,373 · see citing works
(1970) · Cited by 24,983 · see citing works
A New Method for Measuring Daytime Sleepiness: The Epworth Sleepiness Scale
Johns, M. W. (1991) · Sleep · doi:10.1093/sleep/14.6.540 · Cited by 17,364 · see citing works
Eta squared and partial eta squared as measures of effect size in educational research
Richardson, J. T. E. (2011) · Educational Research Review · doi:10.1016/j.edurev.2010.12.001 · Cited by 3,498 · see citing works
Van Dongen, H. P. A., Maislin, G., Mullington, J. M., & Dinges, D. F. (2003) · Sleep · doi:10.1093/sleep/26.2.117 · Cited by 3,173 · see citing works
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996) · Nature · doi:10.1038/379606a0 · Cited by 2,476 · see citing works
Neurocognitive consequences of sleep deprivation
Goel, N., Rao, H., Durmer, J., & Dinges, D. (2009) · Seminars in Neurology · doi:10.1055/s-0029-1237117 · Cited by 2,154 · see citing works
Dinges, D. F., & Powell, J. W. (1985) · Behavior Research Methods, Instruments, & Computers · doi:10.3758/bf03200977 · Cited by 1,750 · see citing works
Inverted-U–Shaped Dopamine Actions on Human Working Memory and Cognitive Control
Cools, R., & D'Esposito, M. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.03.028 · Cited by 1,673 · see citing works
Effects of Sleep Deprivation on Performance: A Meta-Analysis
Pilcher, J. J., & Huffcutt, A. I. (1996) · Sleep · doi:10.1093/sleep/19.4.318 · Cited by 1,549 · see citing works
Neurocognitive Consequences of Sleep Deprivation
Durmer, J. S., & Dinges, D. F. (2005) · Seminars in Neurology · doi:10.1055/s-2005-867080 · Cited by 1,473 · see citing works
Saper, C. B., Fuller, P. M., Pedersen, N. P., Lu, J., & Scammell, T. E. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.032 · Cited by 1,404 · see citing works
A meta-analysis of the impact of short-term sleep deprivation on cognitive variables
Lim, J., & Dinges, D. F. (2010) · Psychological Bulletin · doi:10.1037/a0018883 · Cited by 1,389 · see citing works
<i>Sleep Deprivation and Vigilant Attention</i>
Lim, J., & Dinges, D. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.002 · Cited by 1,213 · see citing works
Dopamine and the regulation of cognition and attention
Nieoullon, A. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00011-4 · Cited by 1,131 · see citing works
Sustained attention performance during sleep deprivation: evidence of state instability.
Doran, S. M., Dongen, H. P. A. V., & Dinges, D. F. (2001) · PubMed · Cited by 801 · see citing works
Dopaminergic Role in Stimulant-Induced Wakefulness
Wisor, J. P., Nishino, S., Sora, I., Uhl, G. R., Mignot, E. J.-M., & Edgar, D. M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01787.2001 · Cited by 762 · see citing works
Dopamine Is a Regulator of Arousal in the Fruit Fly
Kume, K., Kume, S., Park, S. K., Hirsh, J., & Jackson, F. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2048-05.2005 · Cited by 597 · see citing works
VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors
Eban-Rothschild, A., Rothschild, G., Giardino, W. J., Jones, J. R., & de Lecea, L. (2016) · Nature Neuroscience · doi:10.1038/nn.4377 · Cited by 583 · see citing works
Water associated zero maze: a novel rat test for long term traumatic re-experiencing
Ritov, G., & Richter‐Levin, G. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00001 · Cited by 579 · see citing works
Forbes, E. E., Brown, S. M., Kimak, M., Ferrell, R. E., Manuck, S. B., & Hariri, A. R. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002086 · Cited by 408 · see citing works
Dopaminergic Modulation of Arousal in Drosophila
Waldowski, R. A., van Swinderen, B., & Greenspan, R. J. (2005) · Current Biology · doi:10.1016/j.cub.2005.05.025 · Cited by 359 · see citing works
Lo, J. C., Groeger, J. A., Santhi, N., Arbon, E. L., Lazar, A. S., Hasan, S., von Schantz, M., Archer, S. N., & Dijk, D.-J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045987 · Cited by 342 · see citing works
Floresco, S. B. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00062 · Cited by 336 · see citing works
Operation of a homeostatic sleep switch
Pimentel, D. O., Donlea, J. M., Talbot, C. B., Song, S. H., Thurston, A. J. F., & Miesenböck, G. (2016) · Nature · doi:10.1038/nature19055 · Cited by 267 · see citing works
Leproult, R., Colecchia, E. F., Berardi, A., Stickgold, R., Kosslyn, S. M., & Cauter, E. V. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00197.2002 · Cited by 256 · see citing works
Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain
Volkow, N. D., Tomasi, D., Wang, G.-J., Telang, F., Fowler, J. S., Logan, J., Benveniste, H., Kim, R., Thanos, P. K., & Ferré, S. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0045-12.2012 · Cited by 254 · see citing works
Graw, P., Kräuchi, K., Knoblauch, V., Wirz‐Justice, A., & Cajochen, C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2003.12.004 · Cited by 199 · see citing works
Sleep Deprivation Decreases Binding of [11C]Raclopride to Dopamine D2/D3Receptors in the Human Brain
Volkow, N. D., Wang, G., Telang, F., Fowler, J. S., Logan, J., Wong, C., Ma, J., Pradhan, K., Tomasi, D. G., Thanos, P. K., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1443-08.2008 · Cited by 196 · see citing works
Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness
Cajochen, C., Wyatt, J. K., Czeisler, C. A., & Dijk, D. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00209-9 · Cited by 192 · see citing works
Hirvonen, M. M., Laakso, A., Någren, K., Rinne, J. O., Pohjalainen, T., & Hietala, J. (2009) · Synapse · doi:10.1002/syn.20672 · Cited by 176 · cited 1× · see citing works
“The DRD2 gene includes a functional 957 C > T single nucleotide polymorphism (SNP-ID: rs6277) that affects levels and stability of mRNA and has been associated with 15–20% enhanced striatal D 2 receptor availability in C-allele carriers compared to T-allele carriers 43 .”
Sleep Homeostasis and Models of Sleep Regulation
Achermann, P., & Borbély, A. A. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-6645-3.00037-2 · Cited by 140 · see citing works
How do the basal ganglia regulate sleep–wake behavior?
Lazarus, M., Huang, Z., Lu, J., Urade, Y., & Chen, J. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.07.001 · Cited by 137 · see citing works
Oishi, Y., Suzuki, Y., Takahashi, K., Yonezawa, T., Kanda, T., Takata, Y., Chérasse, Y., & Lazarus, M. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1365-7 · Cited by 130 · see citing works
Rétey, J., Adam, M., Gottselig, J. M., Khatami, R., Dürr, R., Achermann, P., & Landolt, H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1538-06.2006 · Cited by 119 · see citing works
Self-citationBodenmann, S., Hohoff, C., Freitag, C. M., Deckert, J., Rétey, J., Bachmann, V., & Landolt, H. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01689.x · Cited by 118 · see citing works
Self-citationModafinil Improves Alertness, Vigilance, and Executive Function During Simulated Night Shifts
Walsh, J. K., Randazzo, A. C., Stone, K., & Schweitzer, P. K. (2004) · SLEEP · doi:10.1093/sleep/27.3.434 · Cited by 115 · see citing works
Wu, M. N., Koh, K., Yue, Z., Joiner, W. J., & Sehgal, A. (2008) · SLEEP · doi:10.1093/sleep/31.4.465 · Cited by 108 · see citing works
Bodenmann, S., Rusterholz, T., Dürr, R., Stoll, C., Bachmann, V., Geißler, E. M., Jaggi-Schwarz, K., & Landolt, H. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1427-09.2009 · Cited by 107 · see citing works
Self-citationFunctional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans
Bachmann, V., Klaus, F., Bodenmann, S., Schäfer, N., Brugger, P., Huber, S., Berger, W., & Landolt, H. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr173 · Cited by 107 · see citing works
Self-citationNumber of Lapses during the Psychomotor Vigilance Task as an Objective Measure of Fatigue
Lee, I.-S., Bardwell, W. A., Ancoli‐Israel, S., & Dimsdale, J. E. (2010) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27766 · Cited by 106 · see citing works
Bertolino, A., Fazio, L., Giorgio, A. D., Blasi, G., Romano, R., Taurisano, P., Caforio, G., Sinibaldi, L., Ursini, G., Popolizio, T., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4858-08.2009 · Cited by 101 · see citing works
Corsi‐Cabrera, M., Arce, C., Ramos, J., Lorenzo, I., & Guevara, M. Á. (1996) · SLEEP · doi:10.1093/sleep/19.7.563 · Cited by 97 · see citing works
Hefti, K., Holst, S. C., Sóvágó, J., Bachmann, V., Buck, A., Ametamey, S. M., Scheidegger, M., Berthold, T., Gomez‐Mancilla, B., Seifritz, E., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.030 · Cited by 93 · see citing works
Self-citationNigrostriatal Dopamine Acting on Globus Pallidus Regulates Sleep
Qiu, M., Yao, Q.-L., Vetrivelan, R., Chen, M. C., & Lu, J. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhu241 · Cited by 89 · see citing works
Effects of Noradrenaline and Dopamine on Supraspinal Fatigue in Well-Trained Men
Klass, M., Roelands, B., Lévénez, M., Fontenelle, V., Pattyn, N., MEEUSEN, R. R., & Duchateau, J. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318265f356 · Cited by 82 · see citing works
Sebban, C., Zhang, X. Q., Tesolin, B., Millan, M. J., & Spedding, M. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702894 · Cited by 82 · see citing works
Costa, A. C. L., Riedel, M. J., Müller, U., Möller, H., & Ettinger, U. (2011) · Synapse · doi:10.1002/syn.20927 · Cited by 78 · see citing works
Dopaminergic Role in Regulating Neurophysiological Markers of Sleep Homeostasis in Humans
Holst, S. C., Bersagliere, A., Bachmann, V., Berger, W., Achermann, P., & Landolt, H. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4128-13.2014 · Cited by 70 · see citing works
Self-citationVolkow, N. D., Tomasi, D. G., Wang, G., Telang, F., Fowler, J. S., Wang, R. L., Logan, J., Wong, C., Jayne, M. C., & Swanson, J. M. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.01.003 · Cited by 68 · see citing works
Lim, J., Ebstein, R. P., Tse, C., Monakhov, M. V., Lai, P. S., Dinges, D. F., & Kwok, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033767 · Cited by 67 · see citing works
Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory
Li, S., Papenberg, G., Nagel, I. E., Preuschhof, C., Schröder, J., Nietfeld, W., Bertram, L., Heekeren, H. R., Lindenberger, U., & Bäckman, L. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.08.001 · Cited by 64 · see citing works
Satterfield, B. C., Wisor, J. P., Field, S. A., Schmidt, M. A., & Dongen, H. P. A. V. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.12.009 · Cited by 55 · see citing works
Common variants in DRD2 are associated with sleep duration: the CARe consortium
Cade, B. E., Gottlieb, D. J., Lauderdale, D. S., Bennett, D. A., Buchman, A. S., Buxbaum, S. G., Jager, P. L. D., Evans, D. S., Fülöp, T., Gharib, S. A., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv434 · Cited by 52 · see citing works
Spencer, T. J., Biederman, J., Faraone, S. V., Madras, B. K., Bonab, A. A., Dougherty, D. D., Batchelder, H., Clarke, A., & Fischman, A. J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.010 · Cited by 51 · see citing works
Sleep Homeostasis, Metabolism, and Adenosine
Holst, S. C., & Landolt, H. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-014-0007-3 · Cited by 50 · see citing works
Self-citationSleep Pharmacogenetics: Personalized Sleep-Wake Therapy
Holst, S. C., Valomon, A., & Landolt, H. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103801 · Cited by 47 · see citing works
Self-citationValomon, A., Holst, S. C., Bachmann, V., Viola, A., Schmidt, C., Zuercher, J., Berger, W., Cajochen, C., & Landolt, H. (2014) · Chronobiology International · doi:10.3109/07420528.2014.896376 · Cited by 43 · see citing works
Self-citationSharp and sleepy: evidence for dissociation between sleep pressure and nocturnal performance
GALLIAUD, E., Taillard, J., Sagaspe, P., Valtat, C., Bioulac, B. H., & Philip, P. (2008) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2008.00629.x · Cited by 41 · see citing works
Greer, S. M., Goldstein‐Piekarski, A. N., Knutson, B. D., & Walker, M. P. (2016) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_00939 · Cited by 27 · see citing works
Maire, M., Reichert, C., Gabel, V., Viola, A., Krebs, J., Strobel, W. M., Landolt, H., Bachmann, V., Cajochen, C., & Schmidt, C. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00059 · Cited by 24 · see citing works
Self-citationClassification of Waking, Sleep Onset and Deep Sleep by Single Measures
Šušmáková, K., & Krakovská, A. (2007) · Cited by 23 · see citing works
Tomasi, D. G., Wang, G.-J., & Volkow, N. D. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.93 · Cited by 22 · see citing works
Jang, H. S., Kim, J. Y., Kim, S., et al. (2009) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2009.13.3.147 · Cited by 11 · see citing works
Goldenberg, F., Weil, J., & von Frenckell, R. (1988) · Neurophysiologie Clinique · doi:10.1016/s0987-7053(88)80054-6 · Cited by 5 · see citing works
The Effects of Dopamine Receptor Agonists on the Sleep-Wake Cycle
Herrera-Solís, A., Arias-Carrión, Ó., Sarro-Ramírez, A., Salas-Crisóstomo, M., & Murillo‐Rodríguez, E. (2016) · Springer eBooks · doi:10.1007/978-3-319-46437-4_3 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Goldenberg F., Weil J. S. & Von Frenckell R. Utilization of theta/alpha spectral range as an indicator of vigilance: pharmacological applications during repeated sleep latency tests. Neurophysiol. Clin. Clinical Neurophysiol. 18, 433– 445 (1988). 3054474
- Herrera-Solís A., Arias-Carrión O., Sarro-Ramírez A., Salas-Crisóstomo M. & Murillo-Rodríguez E. In Dopamine and Sleep (eds Monti J. M., Pandi-Perumal S. R. & Chokroverty S.) 39– 46 (Springer International Publishing, 2016).
- Sturm A., Clarenbach P., Largiadèr F. & Wicki O. Checklisten der aktuellen Medizin, Checkliste Schlafstörungen (Thieme, 1997).
Cited by
Sorted by citations
Sheaves, B., Cropley, V. L., Moseley, P., Woodruff, P. W. R., Punton, G., Speth, C., Speth, J., Meerlo, P., & Brederoo, S. G. (2025) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaf107 · Cited by 6 · see citing works
- Authors
- Holst, S. C., Müller, T., Valomon, A., Seebauer, B., Berger, W., & Landolt, H.-P.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Holst, Sebastian C.
- Venue
- Scientific Reports
- Published
- 2017-04-10
- Volume
- 7
- Issue
- 1
- Pages
- 45982-45982
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5385564
- OpenAlex
- W2606964637
- Cited by
- 45
- References
- 68
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 3
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (135414, 320030)
- Universität Zürich (FK-15-039)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sleep deprivation, dopamine transporter, dopamine D2 receptor, genetic polymorphism, sustained attention, sleepiness, psychomotor vigilance test, EEG spectral power, prolonged wakefulness, dopaminergic signaling
- MeSH terms
- Adult, Behavior, Demography, Dopamine, Electroencephalography, Female, Genotype, Humans, Male, Polymorphism, Genetic, Psychomotor Performance, Sleep Deprivation, Task Performance and Analysis, Wakefulness, Receptors, Dopamine D2, Dopamine Plasma Membrane Transport Proteins, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
