ReviewSleep medicine2017
Connectome and molecular pharmacological differences in the dopaminergic system in restless legs syndrome (RLS): plastic changes and neuroadaptations that may contribute to augmentation.
Review in Sleep medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Pooled it
- Revisiting brain iron deficiency in restless legs syndrome using magnetic resonance imaging.NeuroImage. Clinical · 2022Pooled it
- Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial.Movement disorders : official journal of the Movement Disorder Society · 2017Trial
- Pathophysiology and pharmacological management for sleep problems in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Integration of Brain Proteomes and Genome-Wide Association Data Identifies GLO1 as a Candidate Causal Gene and Therapeutic Target for Restless Legs Syndrome.International journal of molecular sciences · 2026Article
- Adenosine ABiomolecules & therapeutics · 2026Review
- Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.Acta neurologica Belgica · 2025Article
- Review
- Transcriptomic Changes and Pathological Mechanisms in Familial and Sporadic Idiopathic Restless Legs Syndrome: Implications for Inflammation and Cell Adhesion Molecules.Nature and science of sleep · 2025Article
- Exploring the Top 50 Drugs Associated with Restless Legs Syndrome Based on the FDA Data from 2004 to 2024.Nature and science of sleep · 2025Article
- Identification of Causal Genes and Potential Drug Targets for Restless Legs Syndrome: A Comprehensive Mendelian Randomization Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- RLS-associated MEIS transcription factors control distinct processes in human neural stem cells.Scientific reports · 2024Article
- Restless legs syndrome: abbreviated guidelines by the German sleep society and the German neurological society.Neurological research and practice · 2024Article
- Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.PloS one · 2024Article
- Effects of iron-deficient diet on sleep onset and spinal reflexes in a rodent model of Restless Legs Syndrome.Frontiers in neurology · 2023Article
- Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating.PloS one · 2023Article
- Restless legs syndrome: Over 50 years of European contribution.Journal of sleep research · 2022Review
- Chronic testicular pain cured by low-dose pramipexole: is there an association with restless legs syndrome?Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022Article
- Factors associated with augmentation in patients with restless legs syndrome.European journal of neurology · 2022Article
- Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China.Sleep & breathing = Schlaf & Atmung · 2022Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Restless legs syndrome (RLS) is primarily treated with levodopa and dopaminergics that target the inhibitory dopamine receptor subtypes D3 and D2. The initial success of this therapy led to the idea of a hypodopaminergic state as the mechanism underlying RLS. However, multiple lines of evidence suggest that this simplified concept of a reduced dopamine function as the basis of RLS is incomplete. Moreover, long-term medication with the D2/D3 agonists leads to a reversal of the initial benefits of dopamine agonists and augmentation, which is a worsening of symptoms under therapy. The recent findings on the state of the dopamine system in RLS that support the notion that a dysfunction in the dopamine system may in fact induce a hyperdopaminergic state are summarized. On the basis of these data, the concept of a dynamic nature of the dopamine effects in a circadian context is presented. The possible interactions of cell adhesion molecules expressed by the dopaminergic systems and their possible effects on RLS and augmentation are discussed. Genome-wide association studies (GWAS) indicate a significantly increased risk for RLS in populations with genomic variants of the cell adhesion molecule receptor type protein tyrosine phosphatase D (PTPRD), and PTPRD is abundantly expressed by dopamine neurons. PTPRD may play a role in the reconfiguration of neural circuits, including shaping the interplay of G protein-coupled receptor (GPCR) homomers and heteromers that mediate dopaminergic modulation. Recent animal model data support the concept that interactions between functionally distinct dopamine receptor subtypes can reshape behavioral outcomes and change with normal aging. Additionally, long-term activation of one dopamine receptor subtype can increase the receptor expression of a different receptor subtype with opposite modulatory actions. Such dopamine receptor interactions at both spinal and supraspinal levels appear to play important roles in RLS. In addition, these interactions can extend to the adenosine A
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.