{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:26:01Z","timestamp":1791930361161,"version":"4.3.4"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The levels of anxiety and depression among patients with restless leg syndrome (RLS) are controversial. The aim of this systematic review and meta-analysis was to compare the levels of depression and anxiety among individuals with RLS with those of healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an extensive electronic search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from their inception dates to 20 June 2023. Studies presenting data on depression and anxiety in individuals with RLS were included, and a comprehensive meta-analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-one studies matched the inclusion criteria. Significantly more depressive symptoms were present in the individuals with RLS than in those without RLS, as measured by the Beck Depression Inventory [mean difference (MD)\u2009=\u20096.58, 95% confidence interval (CI)\u2009=\u20095.54\u20137.62, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.01; heterogeneity I<jats:sup>2<\/jats:sup>\u2009=\u20090%, <jats:italic>p<\/jats:italic>\u2009=\u20090.99]. Similarly, the results from the Beck Anxiety Inventory indicated that there were significantly more pronounced anxiety symptoms in the individuals with RLS than in those without RLS (MD\u2009=\u20099.30, 95%CI\u2009=\u20097.65\u201310.94, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.01; heterogeneity I<jats:sup>2<\/jats:sup>\u2009=\u20090%, <jats:italic>p<\/jats:italic>\u2009=\u20090.92). The other anxiety and depression scales also yielded statistically significant results. Significant heterogeneity was observed in the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, with the primary contributing factor probably being the scoring criteria of the scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This meta-analysis found that the levels of depression and anxiety symptoms were significantly higher in individuals with RLS than in their healthy counterparts.<\/jats:p><jats:p><jats:bold>Systematic review registration:<\/jats:bold><jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42023410364<\/jats:ext-link>, (identifier CRD42023410364).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1366839","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:39:15Z","timestamp":1710736755000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Associations of anxiety and depression with restless leg syndrome: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Tianyang","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoquan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1212\/CON.0000000000000488","article-title":"Restless legs syndrome and sleep-related movement disorders. Continuum (Minneap Minn)","volume":"23","author":"Trotti","year":"2017","journal-title":"Sleep Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.sleep.2014.03.025","article-title":"Restless legs syndrome\/Willis-Ekbom disease diagnostic criteria: updated international restless legs syndrome study group (IRLSSG) consensus criteria-history, rationale, description, and significance","volume":"15","author":"Allen","year":"2014","journal-title":"Sleep Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1136\/practneurol-2017-001762","article-title":"Restless legs syndrome: clinical features, diagnosis and a practical approach to management","volume":"17","author":"Wijemanne","year":"2017","journal-title":"Pract Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.smrv.2011.05.002","article-title":"Epidemiology of restless legs syndrome: a synthesis of the literature","volume":"16","author":"Ohayon","year":"2012","journal-title":"Sleep Med Rev"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.sleep.2005.03.008","article-title":"Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries","volume":"6","author":"Bjorvatn","year":"2005","journal-title":"Sleep Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1136\/postgradmedj-2012-131634","article-title":"Restless legs syndrome: pathophysiology and modern management","volume":"89","author":"Nagandla","year":"2013","journal-title":"Postgrad Med J"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.sleep.2008.07.004","article-title":"Restless legs syndrome and the five-factor model of personality: results from a community sample","volume":"10","author":"Kalaydjian","year":"2009","journal-title":"Sleep Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.sleep.2006.01.004","article-title":"Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin sleep cohort","volume":"7","author":"Winkelman","year":"2006","journal-title":"Sleep Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"785","DOI":"10.5664\/jcsm.7106","article-title":"Executive and visuospatial dysfunction in patients with primary restless legs syndrome\/Willis-Ekbom disease: study of a Chinese population","volume":"14","author":"Li","year":"2018","journal-title":"J Clin Sleep Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.sleep.2005.05.006","article-title":"Cognitive deficits associated with restless legs syndrome (RLS)","volume":"7","author":"Pearson","year":"2006","journal-title":"Sleep Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1002\/mds.23353","article-title":"Short-term attention and verbal fluency is decreased in restless legs syndrome patients","volume":"25","author":"Fulda","year":"2010","journal-title":"Mov Disord"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2147\/NSS.S236393","article-title":"Prevalence and risk factors of restless legs syndrome in hemodialysis patients","volume":"12","author":"Zhang","year":"2020","journal-title":"Nat Sci Sleep"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2165\/11317500-000000000-00000","article-title":"Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management","volume":"24","author":"Hornyak","year":"2010","journal-title":"CNS Drugs"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s11818-012-0568-7","article-title":"Restless legs syndrome in patients with depressive disorders","volume":"16","author":"Happe","year":"2012","journal-title":"Somnologie"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"102176","DOI":"10.1016\/j.msard.2020.102176","article-title":"Restless legs syndrome, sleep quality, and perceived cognitive impairment in adults with multiple sclerosis","volume":"43","author":"Cederberg","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jsmc.2015.05.017","article-title":"Restless legs syndrome\/Willis-Ekbom disease morbidity: burden, quality of life, cardiovascular aspects, and sleep","volume":"10","author":"Stevens","year":"2015","journal-title":"Sleep Med Clin"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e679","DOI":"10.4088\/JCP.13r08692","article-title":"Mood disorders in restless legs syndrome (Willis-Ekbom disease)","volume":"75","author":"Becker","year":"2014","journal-title":"Clin Psychiatry"},{"key":"ref18","volume-title":"The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses","author":"Wells","year":"2009"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br J Med Psychol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/s0895-4356(01)00377-8","article-title":"Funnel plots for detecting bias in meta-analysis:guidelines on choice of axis","volume":"54","author":"Sterne","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s11325-021-02375-3","article-title":"Evaluation of affective temperament profile and levels of depressive symptoms and anxiety in patients with restless legs syndrome","volume":"26","author":"Basaran","year":"2022","journal-title":"Sleep Breath"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1007\/BFb0026701","article-title":"Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey","volume":"75","author":"Sevim","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.2147\/NDT.S174552","article-title":"Investigation of alexithymia and levels of anxiety and depression among patients with restless legs syndrome","volume":"14","author":"Yilmaz","year":"2018","journal-title":"Neuropsychiatr Dis Treat"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.33588\/rn.6506.2016576","article-title":"Calidad de Vida y caracteristicas asociadas del sindrome de piernas inquietas en la poblacion adulta de Burgos, Espa\u00f1a quality of life and associated characteristics of restless legs syndrome in the adult population of Burgos, Spain","volume":"65","author":"Barroso-Perez","year":"2017","journal-title":"Rev Neurol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4274\/jtsm.galenos.2019.92485","article-title":"Huzursuz Bacaklar Sendromu ve Bili\u015fsel Fonksiyonlar; restless legs syndrome and cognitive functions","volume":"6","author":"Aydin","year":"2019","journal-title":"J Turk Sleep Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s11818-013-0623-z","article-title":"Personality traits in patients with restless legs syndrome","volume":"17","author":"Steinig","year":"2013","journal-title":"Somnologie"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s41105-023-00467-z","article-title":"Evaluation of emotional dysregulation in patients with restless legs syndrome","volume":"21","author":"Kocakaya","year":"2023","journal-title":"Sleep Biol Rhythms"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/23279095.2022.2043326","article-title":"Recognition of emotional face expressions in patients with restless legs syndrome","author":"Mail Gurkan","year":"2022","journal-title":"Appl Neuropsychol Adult"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.17241\/smr.2019.00339","article-title":"Difference in psychological distress between patients with periodic limb movement disorder and restless legs syndrome","volume":"10","author":"Byun","year":"2019","journal-title":"Sleep Med Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"161","DOI":"10.4274\/tnd.04764","article-title":"The prevalence of fibromyalgia in patients with restless legs syndrome","volume":"22","author":"Ylmaz","year":"2016","journal-title":"Turk Noroloji Dergisi"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1111\/head.12382","article-title":"Prevalence of migraine in patients with restless legs syndrome: a case-control study","volume":"54","author":"Fern\u00e1ndez-Matarrubia","year":"2014","journal-title":"Headache"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/s0925-4927(02)00023-9","article-title":"EEG mapping in patients with restless legs syndrome as compared with normal controls","volume":"115","author":"Saletu","year":"2002","journal-title":"Psychiatry Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"548","DOI":"10.3881\/j.issn.1000-503X.2016.05.010","article-title":"Restless legs syndrome in adults in Peking union medical college hospital","volume":"38","author":"Chen","year":"2016","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Ba"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.3390\/jcm9124115","article-title":"Changes in Hepcidin serum levels correlate with clinical improvement in idiopathic restless legs syndrome patients","volume":"9","author":"Im","year":"2020","journal-title":"J Clin Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1080\/15402002.2014.919917","article-title":"Restless legs syndrome: psychiatric comorbidities are more important than neuroticism","volume":"13","author":"Trautmann","year":"2015","journal-title":"Behav Sleep Med"},{"key":"ref37","first-page":"1069","article-title":"Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders","volume":"32","author":"Cho","year":"2009","journal-title":"Sleep"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1111\/ene.12462","article-title":"Association between restless legs syndrome and migraine: a population-based study","volume":"21","author":"Zanigni","year":"2014","journal-title":"Eur J Neurol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1176\/appi.neuropsych.12120394","article-title":"Comparison of cognitive functioning among individuals with treated restless legs syndrome (RLS), untreated RLS, and no RLS","volume":"26","author":"Lee","year":"2014","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"225","DOI":"10.5835\/jecm.omu.31.04.005","article-title":"Restless legs syndrome and depression-anxiety disorder association in iron deficiency anemia patients","volume":"31","author":"Demir","year":"2014","journal-title":"J Exp Clin Med"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/gerona\/glp161","article-title":"Prevalence and clinical correlates of restless legs syndrome in an elderly French population: the synapse study","volume":"65","author":"Celle","year":"2010","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1213\/ANE.0000000000001596","article-title":"Publication Bias: the elephant in the review","volume":"123","author":"Dalton","year":"2016","journal-title":"Anesth Analg"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1590\/0004-282X-ANP-2020-0400","article-title":"Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression","volume":"80","author":"Sevim","year":"2022","journal-title":"Arq Neuropsiquiatr"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1590\/0004-282X20200084","article-title":"Restless legs syndrome\/Willis-Ekbom disease in multiple sclerosis: a contributing factor for anxiety, disability, sleep disorder, and quality of life","volume":"78","author":"Sefero\u011flu","year":"2020","journal-title":"Arq Neuropsiquiatr"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1080\/01616412.2016.1147682","article-title":"Restless leg syndrome: a risk factor of higher prevalence of anxiety and depression in Parkinson's disease patients","volume":"38","author":"Rana","year":"2016","journal-title":"Neurol Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1176\/appi.neuropsych.15090228","article-title":"Mood symptoms and restless legs syndrome without periodic limb movements during sleep: is it a clinical subtype?","volume":"29","author":"Lee","year":"2017","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jpainsymman.2012.06.018","article-title":"Restless legs syndrome as a cause of sleep disturbances in cancer patients receiving chemotherapy","volume":"46","author":"Saini","year":"2013","journal-title":"J Pain Symptom Manag"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s11136-010-9614-8","article-title":"Restless legs syndrome and its relationship with anxiety, depression, and quality of life in cancer patients undergoing chemotherapy","volume":"19","author":"Ostacoli","year":"2010","journal-title":"Qual Life Res"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1093\/sleep\/27.8.1499","article-title":"Symptoms of attention-deficit\/hyperactivity disorder in adults with restless legs syndrome","volume":"27","author":"Wagner","year":"2004","journal-title":"Sleep"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00384-016-2681-8","article-title":"Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life","volume":"32","author":"Schindlbeck","year":"2017","journal-title":"Int J Color Dis"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1007\/s11325-013-0800-0","article-title":"Psychosomatic symptom profiles in patients with restless legs syndrome","volume":"17","author":"Kim","year":"2013","journal-title":"Sleep Breath"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.4088\/jcp.v66n0909","article-title":"Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome","volume":"66","author":"Hornyak","year":"2005","journal-title":"J Clin Psychiatry"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1001\/jama.262.11.1479","article-title":"Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention?","volume":"262","author":"Ford","year":"1989","journal-title":"JAMA"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/s0165-0327(02)00072-1","article-title":"Primary insomnia: a risk factor to develop depression?","volume":"76","author":"Riemann","year":"2003","journal-title":"J Affect Disord"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ijpsycho.2014.12.005","article-title":"Neurocognitive function in patients with idiopathic restless legs syndrome before and after treatment with dopamine-agonist","volume":"95","author":"Galbiati","year":"2015","journal-title":"Int J Psychophysiol"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"994545","DOI":"10.3389\/fendo.2022.994545","article-title":"Correlation between vitamin D and poor sleep status in restless legs syndrome","volume":"13","author":"Geng","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1016\/j.sleep.2014.05.009","article-title":"Altered brain iron homeostasis and dopaminergic function in restless legs syndrome (Willis\u2013Ekbom disease)","volume":"15","author":"Earley","year":"2014","journal-title":"Sleep Med"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1007\/s13311-021-01019-4","article-title":"Restless legs syndrome: contemporary diagnosis and treatment","volume":"18","author":"Gossard","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1212\/wnl.52.5.932","article-title":"Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies","volume":"52","author":"Turjanski","year":"1999","journal-title":"Neurology"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/BF03351014","article-title":"Circadian variation in plasma dopamine levels in man","volume":"7","author":"Sowers","year":"1984","journal-title":"J Endocrinol Investig"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41467-022-28190-2","article-title":"NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model","volume":"13","author":"Qi","year":"2022","journal-title":"Nat Commun"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1093\/ijnp\/pyx056","article-title":"Dopamine system dysregulation in major depressive disorders","volume":"20","author":"Belujon","year":"2017","journal-title":"Int J Neuropsychopharmacol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1366839\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:40:33Z","timestamp":1710736833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1366839\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":62,"alternative-id":["10.3389\/fneur.2024.1366839"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1366839","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]},"article-number":"1366839"}}