title: Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome.
abstract: Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess. While it is not known how these changes in dopamine or iron produce the symptoms of RLS, genetic and hormone studies of RLS have identified other biologic systems or genes, such as the endogenous opioid and melanocortin systems and BTBD9 and MEIS1, that may explain some of the iron or dopamine changes in relation to RLS. This manuscript will review what is known about the pathophysiology of RLS, especially as it relates to changes in iron, dopamine, genetics, and hormonal systems.
authors.affiliation: Lippard Laboratory of Clinical Investigation, Division of Movement Disorders, Department of Neurology, Yale University School of Medicine, Room 710, West Haven VAMC, 950 Campbell Avenue, West Haven, CT, 06516, USA.
authors.forename: Farhan H
authors.initials: FH
authors.lastname: Khan
authors.affiliation: Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
authors.forename: Caitlyn D
authors.initials: CD
authors.lastname: Ahlberg
authors.affiliation: Lippard Laboratory of Clinical Investigation, Division of Movement Disorders, Department of Neurology, Yale University School of Medicine, Room 710, West Haven VAMC, 950 Campbell Avenue, West Haven, CT, 06516, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chow
authors.affiliation: Lippard Laboratory of Clinical Investigation, Division of Movement Disorders, Department of Neurology, Yale University School of Medicine, Room 710, West Haven VAMC, 950 Campbell Avenue, West Haven, CT, 06516, USA.
authors.forename: Divya R
authors.initials: DR
authors.lastname: Shah
authors.affiliation: Lippard Laboratory of Clinical Investigation, Division of Movement Disorders, Department of Neurology, Yale University School of Medicine, Room 710, West Haven VAMC, 950 Campbell Avenue, West Haven, CT, 06516, USA. Brian.koo@yale.edu.|Connecticut Veterans Affairs Medical Center, 950 Campbell Avenue, West Haven, CT, 06516, USA. Brian.koo@yale.edu.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Koo
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D012148:Restless Legs Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D006728:Hormones; D007501:Iron; D004298:Dopamine
keywords: Dopamine; Genetics; Iron; Pathophysiology; Restless legs syndrome