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Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans.

ABSTRACT: While dopamine affects fundamental brain processes such as movement control, emotional responses, addiction, and pain, the roles for this neurotransmitter in regulating wakefulness and sleep are incompletely understood. Genetically modified animal models with reduced dopamine clearance exhibit hypersensitivity to caffeine, reduced-responsiveness to modafinil, and increased homeostatic response to prolonged wakefulness when compared with wild-type animals. Here we studied sleep-wake regulation in humans and combined pharmacogenetic and neurophysiologic methods to analyze the effects of the 3'-UTR variable-number-tandem-repeat polymorphism of the gene (DAT1, SLC6A3) encoding dopamine transporter (DAT). Previous research demonstrated that healthy homozygous 10-repeat (10R/10R) allele carriers of this genetic variant have reduced striatal DAT protein expression when compared with 9-repeat (9R) allele carriers. Objective and subjective estimates of caffeine sensitivity were higher in 10R allele homozygotes than in carriers of the 9R allele. Moreover, caffeine and modafinil affected wakefulness-induced changes in functional bands (delta, sigma, beta) of rhythmic brain activity in wakefulness and sleep in a DAT1 genotype-dependent manner. Finally, the sleep deprivation-induced increase in well established neurophysiologic markers of sleep homeostasis, including slow-wave sleep, electroencephalographic slow-wave activity (0.5-4.5 Hz), and number of low-frequency (0.5-2.0 Hz) oscillations in non-rapid-eye-movement sleep, was significantly larger in the 10R/10R genotype than in the 9R allele carriers of DAT1. Together, the data suggest that the dopamine transporter contributes to homeostatic sleep-wake regulation in humans.

SUBMITTER: Holst SC

PROVIDER: S-EPMC6608156 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans.

Holst Sebastian C SC Bersagliere Alessia A Bachmann Valérie V Berger Wolfgang W Achermann Peter P Landolt Hans-Peter HP

The Journal of neuroscience : the official journal of the Society for Neuroscience 20140101 2

While dopamine affects fundamental brain processes such as movement control, emotional responses, addiction, and pain, the roles for this neurotransmitter in regulating wakefulness and sleep are incompletely understood. Genetically modified animal models with reduced dopamine clearance exhibit hypersensitivity to caffeine, reduced-responsiveness to modafinil, and increased homeostatic response to prolonged wakefulness when compared with wild-type animals. Here we studied sleep-wake regulation in ...[more]

PMID: 24403155

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Project description:The substantial body of research employing subjective measures indicates that burnout syndrome is associated with cognitive and emotional dysfunctions. The growing amount of neurophysiological and neuroimaging research helps in broadening existing knowledge of the neural mechanisms underlying core burnout components (emotional exhaustion and depersonalization/cynicism) that are inextricably associated with emotional processing. In the presented EEG study, a group of 93 participants (55 women; mean age = 35.8) were selected for the burnout group or the demographically matched control group on the basis of the results of the Maslach Burnout Inventory - General Survey (MBI-GS) and the Areas of Worklife Survey (AWS). Subjects then participated in an EEG experiment using two experimental procedures: a facial recognition task and viewing of passive pictures. The study focuses on analyzing event-related potentials (ERPs): N170, VPP, EPN, and LPP, as indicators of emotional information processing. Our results show that burnout subjects, as compared to the control group, demonstrate significantly weaker response to affect-evoking stimuli, indexed by a decline in VPP amplitude to emotional faces and decreased EPN amplitude in processing emotional scenes. The analysis of N170 and LPP showed no significant between-group difference. The correlation analyses revealed that VPP and EPN, which are ERP components related to emotional processing, are associated with two core burnout symptoms: emotional exhaustion and cynicism. To our knowledge, we are one of the first research groups to use ERPs to demonstrate such a relationship between neurophysiological activity and burnout syndrome in the context of emotional processing. Thus, in conclusion we emphasized that the decreased amplitude of VPP and EPN components in the burnout group may be a neurophysiological manifestation of emotional blunting and may be considered as neurophysiological markers of emotional exhaustion and cynicism. Additionally, we did not observe a decrease in LPP, which may be considered as a marker that significantly differentiates burnout from depression.

Dataset Information

Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans.

Publications

Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans.

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